Top 10 Best Zombie Movies

After being practically dead and buried in the 90s, zombie films have sprung back to life in the last few years.
So let’s stagger moaning through the annals of film history and put together a list of the… Top 10 Best Zombie Movies ever made.

 10. Dawn Of The Dead (2004)
Gone is the subtext, gone is the joy of living in a mall, gone is the subtle character development, but this remake does do a number of things very well. It’s fast, it’s scary and there’s no denying it brought the genre up to date, turning it into something cool and mainstream – no mean feat. It has perhaps the most terrifying opening 10 minutes of any zombie film.

 9. Return Of The Living Dead (1985)
 Ever wonder where zombies got their taste for ‘Braaaiinnns?” It was this movie that introduced it Written and directed by the screenwriter of Alien and Total Recall, this parody of Night Of The Living Dead is so unique and inventive it feels like it’s own creation. The plot sees the dead of Louisville, Kentucky brought back to life by a toxic gas and going on a rampage, for brains.


8. Day Of The Dead (1985)
George A. Romero’s underrated Day takes a microcosm of society and observes how a lack of human communication leads to breakdown. Soon it’s mad scientist vs insane military captain, with everyone else stuck in the middle. And in Capt. Rhodes it features one of the most magnificent bastards ever to grace the screen -Day has the most realistic gore effects in any zombie movie to date, thanks to an absence of cgi and to a Tom Savini at the height of his powers – the headless body on the Dr.’s slab is a magician’s magic trick. Romero considers it to be his best zombie film.

 7. Dead Alive (aka Braindead) (1992)
 The cult horror-comedy from Peter Jackson almost implodes under its own manic loonacy but as a screwball take on Night Of The Living Dead it somehow holds itself together with an endless stream of “did they just do that?” moments. Probably the zombie movie most likely to make you vomit, especially if you don’t like what’s in the custard.


6. White Zombie (1932)
The film that created the zombie genre, before Romero re-imagined the rules three decades later. Zombies used to have a master controlling them, and didn’t eat people. Here the great Béla Lugosi plays a voodoo master in Haiti who turns people into zombies with the power of his mind. Now that’s badass. He also has a no-messing first name – ‘Murder’. Rob Zombie’s heavy metal band White Zombie took the movie’s title as a tribute.

 

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Top 10 Best Zombie Movies

14.08.09 # Top Ten # 174 Comments After being practically dead and buried in the 90s, zombie films have sprung back to life in the last few years.
So let’s stagger moaning through the annals of film history and put together a list of the… Top 10 Best Zombie Movies ever made.
10. Dawn Of The Dead (2004)

Gone is the subtext, gone is the joy of living in a mall, gone is the subtle character development, but this remake does do a number of things very well. It’s fast, it’s scary and there’s no denying it brought the genre up to date, turning it into something cool and mainstream – no mean feat. It has perhaps the most terrifying opening 10 minutes of any zombie film.
9. Return Of The Living Dead (1985)
Ever wonder where zombies got their taste for ‘Braaaiinnns?” It was this movie that introduced it -

Written and directed by the screenwriter of Alien and Total Recall, this parody of Night Of The Living Dead is so unique and inventive it feels like it’s own creation. The plot sees the dead of Louisville, Kentucky brought back to life by a toxic gas and going on a rampage, for brains.
8. Day Of The Dead (1985)
George A. Romero’s underrated Day takes a microcosm of society and observes how a lack of human communication leads to breakdown. Soon it’s mad scientist vs insane military captain, with everyone else stuck in the middle. And in Capt. Rhodes it features one of the most magnificent bastards ever to grace the screen -

Day has the most realistic gore effects in any zombie movie to date, thanks to an absence of cgi and to a Tom Savini at the height of his powers – the headless body on the Dr.’s slab is a magician’s magic trick. Romero considers it to be his best zombie film.
7. Dead Alive (aka Braindead) (1992)

The cult horror-comedy from Peter Jackson almost implodes under its own manic loonacy but as a screwball take on Night Of The Living Dead it somehow holds itself together with an endless stream of “did they just do that?” moments. Probably the zombie movie most likely to make you vomit, especially if you don’t like what’s in the custard.
6. White Zombie (1932)
The film that created the zombie genre, before Romero re-imagined the rules three decades later. Zombies used to have a master controlling them, and didn’t eat people. Here the great Béla Lugosi plays a voodoo master in Haiti who turns people into zombies with the power of his mind. Now that’s badass. He also has a no-messing first name – ‘Murder’. Rob Zombie’s heavy metal band White Zombie took the movie’s title as a tribute.

5. Zombieland (2009)
Imagine a young neurotic Woody Allen in a zombie crisis. That’s effectively who Jesse Eisenberg is playing in this comedy road trip, staying alive by following his carefully formulated rules. Zombieland doesn’t explore the origins of the zombie outbreak or have a particularly interesting plot (Woody Harrelson is trying to find a twinkie), but wins over through the sheer chemistry of its leads, witty writing and an entertaining mystery cameo.

 4. 28 Days Later (2002)
The debate over whether these are zombies or not can rage on, but it’s worth noting just because you change a couple of rules doesn’t mean you’ve created a new genre, the zombie rules have been changing since White Zombie in the 1930s. They didn’t even used to eat people. What 28 Days Later does show is how much one simple change (they can run) can revitalise everything. Add to that the brilliant drama, atmosphere and the haunting scenes of an empty London and you have a movie that stays in the mind long after it’s over.

3. Shaun Of The Dead (2004)
It’s extremely rare that a movie can successfully bridge horror and comedy but Shaun Of The Dead smacks that challenge round the face with a cricket bat. It’s the hum-drum everyday reality of Shaun and Ed’s lives – playing TimeSplitters 2, popping to the shops for a Cornetto – that makes the introduction of blood-drenched zombies feel all the more real and unsettling.

 2. Night Of The Living Dead (1968)
 Romero’s first outing revolutionised the horror genre and the concept of zombies, in a way that is still being felt today. ‘Zombies’ became an undead horde who feasted on the living, dressed in work clothes or casket attire, sported injuries, and shuffled. Gore was introduced too. With its none too subtle references to the war in Vietnam, graphic violence and stark black and white photography, it caused a humongous stir on its initial release and while the violence may seem watered down by current standards it still remains the movie that created the modern zombie.
And here it is, the number 1 all time top zombie movie -

 1. Dawn Of The Dead (1978)
 With its sly take on brainless consumerism, unique atmosphere, assured director, and imaginatively gruesome FX from Tom Savini, this isn’t just the best of Romero’s ‘Dead’ series, but the best zombie movie period. At its core it taps into two desires none of us quite realised we had – to live in a mall where everything is free, and to take down a slow moving enemy with creative weapon combinations. Overall, Dawn Of The Dead is proof that a gore-fest can be thought-provoking and work on multiple levels.

Trail Medication for Brain Cancer Stage 4

This following blog is near and dear to me.  My father was diagnosed last May/June with a highly aggressive brain tumor. He has done a few different treatments including two different surgeries to remove the cancer grow and regrowth.  the information in this blog is to help others that may have no other options. Please note this is  not a cure it is just to help slow down or stop the growth. I have included the steps of how the trial phase is run and the drug information as best to my ability.  This medication is still in its Trial phases and my father has has good results. Some trials may also be done with slightly different med combinations.  Please feel free to comment or ask questions.

May is National Brain Tumor Awareness Month

Brain tumors do not discriminate. Primary brain tumors – those that begin in the brain and tend to stay in the brain – occur in people of all ages, but they are statistically more frequent in children and older adults. Metastatic brain tumors – those that begin as a cancer elsewhere in the body and spread to the brain – are more common in adults than in children. Metastatic brain tumors are the most common brain tumor, with an annual incidence more than four times greater than that of primary brain tumors. Cancers that most commonly metastasize to the brain are lung and breast. In the United States, an estimated 61,414 new cases of primary brain tumors are expected to be diagnosed in 2009. Of this total number, an estimated 37% will be malignant and 63% will be benign.

Avastin and Tarceva (Erlotinib) Trial - Malignant Gliomas:

 A PHASE II STUDY OF AVASTIN® (Bevacizumab) AND TARCEVA® (Erlotinib) AFTER RADIATION THERAPY AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME WITHOUT MGMT PROMOTER METHYLATION (IRB #19965)

 

Malignant gliomas are the most common brain tumor in adults with about 15,000-17,000 new cases each year in the United States. The typical median survival is approximately 12 months for patients with newly diagnosed glioblastoma (GBM) and 24-36 months for patients with anaplastic astrocytoma. Current standard therapy can treat this type of cancer but in most cases the tumor returns. Standard therapy is radiation therapy combined with temozolomide. This treatment works best for patients who have a certain gene called MGMT turned "off" (methylated).

This study involves the combination of radiation therapy and temzolomide as part of normal standard therapy. The patient's tumor will be tested for MGMT status. If the MGMT gene is not turned "off", subjects will be treated with Avastin (which inhibits blood vessel growth) and Erlotinib (Tarceva--which inhibits a receptor called EGFR). If the MGMT gene is turned "off", subjects will receive standard of care therapy.

Avastin has been approved by the Food and Drug Administration (FDA) for colon cancer, breast cancer, and lung cancer and has reported activity in brain tumors. Erlotinib has been approved by the FDA for lung cancer and pancreatic cancer. Avastin and Erlotinib have not yet been approved by the FDA for glioblastoma and are considered investigational. The purpose of this study is too evaluated whether this combination is better than maintenance with temozolomide after radiation therapy.

Once a patient signs the main consent form, tissue used to confirm diagnosis or surgery will be sent for MGMT analysis to determine whether or not the gene is "on" or "off". Please note, patients who do not have tissue available for central review will not be eligible to participate in this study. While this analysis is taking place, subjects will begin standard treatment (with radiation and temozolomide) for 7 weeks. Once the 7 week standard therapy is complete, subjects will have an MRI done. If the results of the MRI show that the tumor has remained stable or has decreased in size, the subject may continue on trial. If the tumor has grown, subjects will not be allowed to participate in this trial. It is at this point that the analysis of the MGMT gene in the tumor will be shared with the subject. If the MGMT gene is not active in the subject's tumor, the subject will be removed from the study and will continue to receive standard of care treatment for their condition. If the MGMT gene is active in the subject's tumor, the subject will be given Avastin every 2 weeks as an intravenous infusion (over 30-90 minutes) and will take Erlotinib orally daily. Patients will remain on the study for up to one year as long as the study treatment is working. The following procedures will also be done during subject's participation in this trial:

• A pregnancy test (if female of childbearing potential) will be done before the first cycle of treatment. A blood sample (about 1 teaspoon of 5 mL) will be taken
• Electrocardiogram (EKG—a test that measures the electrical activity of the heart) may be done before first cycle if deemed medically necessary by the study doctor.
• Neurological exam (including blood pressure and heart rate) will be done on Day 1 of each cycle.
• Urine test will be done Day 1 of each cycle.
• Blood test (approximately 2-3 teaspoons or 10-15 mL) will be done Day 1 of each cycle.
• Subjects will be asked to record any side effects they experience
• MRI with contrast (including optional MR Perfusion) will be performed every 2 cycles.

Approximately 10 subjects will take part in this research study at Cedars-Sinai. A total of 50 subjects will participate in the study nationwide. Please note that the subject and their insurance company will not be charged for the study drugs (Avastin and Erlotinib) given in this trial. However, while the study team will supply the subject with these drugs, the subject or their insurance company will be responsible to pay for the administration of Avastin. Depending on the time frame of the subject's enrollment, there may be one MRI that falls outside of standard of care procedures. If this is the case, the MRI will be considered a research related procedure and will not be charged to the subject or their insurance company. All other procedures are considered standard of care and will be billed to the subject or their insurance company.

Patients will be followed-up by the study doctor and staff every 3 months until death, if possible. These follow-up visits are considered standard of care. If a patient chooses to no longer come into the clinic, a member of the study staff will call the patient to determine survival.

®
as dyspnea, cough and fever occur. Discontinue TARCEVA if ILD is diagnosed. (5.1) •    Cases of acute renal failure (including fatalities), and renal insufficiency have been reported.
Interrupt TARCEVA in the event of dehydration. Monitor renal function and electrolytes in patients
at risk of dehydration. (5.2) •    Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported.
Monitor periodic liver function testing. Interrupt or discontinue TARCEVA if liver function changes
are severe. (5.3) •    Monitor patients with hepatic impairment closely. Interrupt or discontinue TARCEVA if changes in
liver function are severe (5.4) •    Gastrointestinal perforations, including fatalities, have been reported. Discontinue TARCEVA. (5.5) •    Bullous and exfoliative skin disorders, including fatalities, have been reported. Interrupt or
discontinue TARCEVA (5.6) •    Myocardial infarction/ischemia has been reported, including fatalities, in patients with pancreatic
cancer. (5.7) •    Cerebrovascular accidents, including a fatality, have been reported in patients with pancreatic
cancer. (5.8) •    Microangiopathic Hemolytic Anemia with thrombocytopenia has been reported in patients with
pancreatic cancer. (5.9) •    Corneal perforation and ulceration have been reported. Interrupt or discontinue TARCEVA (5.10) •    International Normalized Ratio (INR) elevations and bleeding events, some associated with
concomitant warfarin administration have been reported. Monitor patients taking warfarin or other
coumarin-derivative anticoagulants. (5.11) •    TARCEVA can cause fetal harm when administered to a pregnant woman. Women should be
advised to avoid pregnancy while on TARCEVA. (5.12)
--------------------------------ADVERSE REACTIONS---------------------------------
•    The most common adverse reactions (>20%) in maintenance treatment are rash-like events and diarrhea. (6)
•    The most common adverse reactions (>20%) in 2nd line NSCLC are rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, infection and vomiting. (6)
•    The most common adverse reactions (>20%) in pancreatic cancer are fatigue, rash, nausea, anorexia, diarrhea, abdominal pain, vomiting, weight decrease, infection, edema, pyrexia, constipation, bone pain, dyspnea, stomatitis and myalgia. (6)
To report SUSPECTED ADVERSE REACTIONS, contact OSI Pharmaceuticals Inc. at 1-800-572-1932 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
--------------------------------DRUG INTERACTIONS---------------------------------
•    CYP3A4 inhibitors may increase erlotinib plasma concentrations. (7) •    CYP3A4 inducers may decrease erlotinib plasma concentrations. (7) •    CYP1A2 inducers may decrease erlotinib plasma concentrations. (7) •    Erlotinib solubility is pH dependent. Drugs that alter the pH of the upper GI tract may alter the
solubility of erlotinib and hence its absorption. (7) •    Cigarette smoking decreases erlotinib plasma concentrations (7)
See 17 for PATIENT COUNSELING INFORMATION. Revised: [4/2010]
7    DRUG INTERACTIONS
8    USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.3    Nursing Mothers 8.4    Pediatric Use 8.5    Geriatric Use 8.6    Gender 8.7    Race 8.8    Patients with Hepatic Impairment 8.9    Patients with Renal Impairment
10    OVERDOSAGE
11    DESCRIPTION
12    CLINICAL PHARMACOLOGY
12.1    Mechanism of Action 12.3    Pharmacokinetics
13    NONCLINICAL TOXICOLOGY
13.1    Carcinogenesis, Mutagenesis, Impairment of Fertility
14    CLINICAL STUDIES
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TARCEVA safely and effectively. See full prescribing information for TARCEVA.
TARCEVA® (erlotinib) tablets, oral Initial U.S. Approval: 2004
----------------------------RECENT MAJOR CHANGES---------------------------
Indications and Usage (1.1) Warnings and Precautions, Gastrointestinal Perforation (5.5) Warnings and Precautions, Bullous Skin Disorders (5.6) Warnings and Precautions, Ocular Disorders (5.10)
04/2010 04/2009 04/2009 04/2009
-------------------------------INDICATIONS AND USAGE-----------------------------
TARCEVA is a kinase inhibitor indicated for:
•
•
•
Maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. (1.1) Treatment of locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. (1.1) First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. (1.2)
--------------------------DOSAGE AND ADMINISTRATION---------------------------
•    The dose for NSCLC is 150 mg/day. (2.1) •    The dose for pancreatic cancer is 100 mg/day. (2.2) •    All doses of TARCEVA should be taken on an empty stomach at least one hour before or two hours
after food. (2.1, 2.2)
•    Reduce in 50 mg decrements, when necessary. (2.3)
------------------------DOSAGE FORMS AND STRENGTHS-------------------------
•    Tablets: 25 mg, 100 mg and 150 mg. (3)
---------------------------------CONTRAINDICATIONS--------------------------------
•    None. (4)
--------------------------WARNINGS AND PRECAUTIONS---------------------------
•    Interstitial Lung Disease (ILD)-like events, including fatalities have been infrequently reported. Interrupt TARCEVA if acute onset of new or progressive unexplained pulmonary symptoms, such
FULL PRESCRIBING INFORMATION: CONTENTS *
1    INDICATIONS AND USAGE
1.1    Non-Small Cell Lung Cancer (NSCLC) 1.2    Pancreatic Cancer
2    DOSAGE AND ADMINISTRATION
2.1 2.2 2.3
Recommended Dose – NSCLC Recommended Dose – Pancreatic Cancer Dose Modifications
3    DOSAGE FORMS AND STRENGTHS
4    CONTRAINDICATIONS
5    WARNINGS AND PRECAUTIONS
5.1    Pulmonary Toxicity 5.2    Renal Failure 5.3    Hepatotoxicity 5.4    Patients with Hepatic Impairment 5.5    Gastrointestinal perforation
5.6    Bullous and exfoliative skin disorders 5.7    Myocardial infarction/ischemia 5.8    Cerebrovascular accident 5.9    Microangiopathic Hemolytic Anemia with Thrombocytopenia 5.10    Ocular Disorders
5.11    Elevated International Normalized Ratio and Potential Bleeding 5.12    Use in Pregnancy
6    ADVERSE REACTIONS
6.1    Clinical Trial Experience 6.2    Post-Marketing Experience
FULL PRESCRIBING INFORMATION
1    INDICATIONS AND USAGE
1.1    Non-Small Cell Lung Cancer (NSCLC)
TARCEVA monotherapy is indicated for the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease has not progressed after four cycles of platinum- based first-line chemotherapy [see Clinical Studies (14.1)]. TARCEVA monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen [see Clinical Studies (14.2)].
Results from two, multicenter, placebo-controlled, randomized, Phase 3 trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of TARCEVA with platinum-based chemotherapy [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting [see Clinical Studies (14.3)].
1.2    Pancreatic Cancer
TARCEVA in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer [see Clinical Studies (14.4)].
2    DOSAGE AND ADMINISTRATION
2.1 NSCLC
The recommended daily dose of TARCEVA for NSCLC is 150 mg taken on an empty stomach at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs. There is no evidence that treatment beyond progression is beneficial.
14.1
14.2 14.3 14.4
Non-Small Cell Lung Cancer (NSCLC) – TARCEVA monotherapy administered as maintenance treatment NSCLC – TARCEVA administered as a Single-agent NSCLC – TARCEVA Administered Concurrently with Chemotherapy
Pancreatic Cancer – TARCEVA Administered Concurrently with Gemcitabine
16    HOW SUPPLIED/STORAGE AND HANDLING 17    PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed.
2.2    Pancreatic Cancer
The recommended daily dose of TARCEVA for pancreatic cancer is 100 mg taken on an empty stomach at least one hour before or two hours after the ingestion of food, in combination with gemcitabine [see Clinical Studies (14.4) or the gemcitabine package insert]. Treatment should continue until disease progression or unacceptable toxicity occurs.
2.3    Dose Modifications
In patients who develop an acute onset of new or progressive pulmonary symptoms, such as dyspnea, cough or fever, treatment with TARCEVA should be interrupted pending diagnostic evaluation. If Interstitial Lung Disease (ILD) is diagnosed, TARCEVA should be discontinued and appropriate treatment instituted as necessary [see Warnings and Precautions (5.1)]. Discontinue TARCEVA for hepatic failure or gastrointestinal perforation. Interrupt or discontinue TARCEVA in patients with dehydration who are at risk for renal failure, in patients with severe bullous, blistering or exfoliative skin conditions, or in patients with acute/worsening ocular disorders [see Warnings and Precautions (5.2, 5.3, 5.4, 5.5, 5.6, 5.10)]. Diarrhea can usually be managed with loperamide. Patients with severe diarrhea who are unresponsive to loperamide or who become dehydrated may require dose reduction or temporary interruption of therapy. Patients with severe skin reactions may also require dose reduction or temporary interruption of therapy. When dose reduction is necessary, the TARCEVA dose should be reduced in 50 mg decrements.
In patients who are taking TARCEVA with a strong CYP3A4 inhibitor such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice, a dose reduction should be considered if severe adverse reactions occur. Similarly, in patients who are taking TARCEVA with an inhibitor of both CYP3A4 and CYP1A2 like ciprofloxacin, a dose reduction of TARCEVA should be considered if severe adverse reactions occur [see Drug Interactions (7)].

 Pre-treatment with the CYP3A4 inducer rifampicin decreased erlotinib AUC by about 2/3 to 4/5. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, an increase in the dose of TARCEVA should be considered as tolerated at two week intervals while monitoring the patient’s safety. The maximum dose of TARCEVA studied in combination with rifampicin is 450 mg. If the TARCEVA dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John’s Wort. These too should be avoided if possible [see Drug Interactions (7)]. Cigarette smoking has been shown to reduce erlotinib exposure. Patients should be advised to stop smoking. If a patient continues to smoke, a cautious increase in the dose of TARCEVA, not exceeding 300 mg may be considered, while monitoring the patient’s safety. However, efficacy and long-term safety (> 14 days) of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes. If the TARCEVA dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking [see Clinical Pharmacology (12.3)]. Erlotinib is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh B), patients with hepatic impairment (total bilirubin > ULN or Child-Pugh A, B and C) should be closely monitored during therapy with TARCEVA [see Warnings and Precautions (5.4)]. Treatment with TARCEVA should be used with extra caution in patients with total bilirubin > 3 x ULN. TARCEVA dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range. In the setting of worsening liver function
tests, before they become severe, dose interruption and/or dose reduction with frequent liver function test monitoring should be considered. TARCEVA dosing should be interrupted or discontinued if total bilirubin is >3 x ULN and/or transaminases are >5 x ULN in the setting of normal pretreatment values [see Warnings and Precautions (5.3, 5.4), Adverse Reactions (6.1, 6.2) and Use in Specific Populations (8.8].
3    DOSAGE FORMS AND STRENGTHS
25 mg tablets White film-coated tablets for daily oral administration. Round, biconvex face and straight sides, white film-coated, printed in orange with a “T” and “25” on one side and plain on the other side. 100 mg tablets White film-coated tablets for daily oral administration. Round, biconvex face and straight sides, white film-coated, printed in gray with “T” and “100” on one side and plain on the other side. 150 mg tablets White film-coated tablets for daily oral administration. Round, biconvex face and straight sides, white film-coated, printed in maroon with “T” and “150” on one side and plain on the other side.
5.8    Cerebrovascular Accident
In the pancreatic carcinoma trial, six patients in the TARCEVA/gemcitabine group developed cerebrovascular accidents (incidence: 2.3%). One of these was hemorrhagic and was the only fatal event. In comparison, in the placebo/gemcitabine group there were no cerebrovascular accidents.
5.9    Microangiopathic Hemolytic Anemia with Thrombocytopenia
In the pancreatic carcinoma trial, two patients in the TARCEVA/gemcitabine group developed microangiopathic hemolytic anemia with thrombocytopenia (incidence: 0.8%). Both patients received TARCEVA and gemcitabine concurrently. In comparison, in the placebo/gemcitabine group there were no cases of microangiopathic hemolytic anemia with thrombocytopenia.
5.10    Ocular Disorders
Corneal perforation or ulceration have been reported during use of TARCEVA. Other ocular disorders including abnormal eyelash growth, keratoconjunctivitis sicca or keratitis have been observed with TARCEVA treatment and are known risk factors for corneal ulceration/perforation [see Adverse Reactions (6.1)]. Interrupt or discontinue TARCEVA therapy if patients present with acute/worsening ocular disorders such as eye pain.
5.11    Elevated International Normalized Ratio and Potential Bleeding
International Normalized Ratio (INR) elevations and infrequent reports of bleeding events, including gastrointestinal and non-gastrointestinal bleeding, have been reported in clinical studies, some associated with concomitant warfarin administration. Patients taking warfarin or other coumarin- derivative anticoagulants should be monitored regularly for changes in prothrombin time or INR [see Adverse Reactions (6.1)].
5.12    Use in Pregnancy
TARCEVA can cause fetal harm when administered to a pregnant woman. Erlotinib administered to rabbits during organogenesis at doses that result in plasma drug concentrations of approximately 3 times those in humans at the recommended dose of 150 mg daily, was associated with embryofetal lethality and abortion. When erlotinib was administered to female rats prior to mating and through the first week of pregnancy, at doses 0.3 or 0.7 times the clinical dose of 150 mg, on a mg/m2 basis, there was an increase in early resorptions that resulted in a decrease in the number of live fetuses [see Use in Specific Populations (8.1)]. There are no adequate and well-controlled studies in pregnant women using TARCEVA. Women of childbearing potential should be advised to avoid pregnancy while on TARCEVA. Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy. If TARCEVA is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
6    ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Safety evaluation of TARCEVA is based on more than 1200 cancer patients who received TARCEVA as monotherapy, more than 300 patients who received TARCEVA 100 or 150 mg plus gemcitabine, and 1228 patients who received TARCEVA concurrently with other chemotherapies. There have been reports of serious events, including fatalities, in patients receiving TARCEVA for treatment of NSCLC, pancreatic cancer or other advanced solid tumors [see Warnings and Precautions (5) and Dosage and Administration (2.3)].
6.1    Clinical Trial Experience
Non-Small Cell Lung Cancer
Maintenance Study
Adverse reactions, regardless of causality, that occurred in at least 3% of patients treated with single- agent TARCEVA at 150 mg and at least 3% more often than in the placebo group in the randomized maintenance trial are summarized by NCI-CTC (version 3.0) Grade in Table 1. The most common adverse reactions in patients receiving single-agent TARCEVA 150 mg were rash and diarrhea. Grade 3/4 rash and diarrhea occurred in 6.0% and 1.8%, respectively, in TARCEVA-treated patients. Rash and diarrhea resulted in study discontinuation in 1.2% and 0.5% of TARCEVA-treated patients, respectively. Dose reduction or interruption for rash and diarrhea was needed in 5.1% and 2.8% of patients, respectively. In TARCEVA-treated patients who developed rash, the onset was within two weeks in 66% and within one month in 81%.
Table 1:    NSCLC Maintenance Study: Adverse Reactions Occurring More Frequently (≥ 3%) in the Single-Agent TARCEVA Group than in the Placebo Group and in ≥ 3% of Patients in the TARCEVA Group.
Liver function test abnormalities (including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin) were observed in patients receiving single-agent TARCEVA 150 mg in the Maintenance study. Grade 2 (>2.5 – 5.0 x ULN) ALT elevations occurred in 2% and 1%, and Grade 3 (>5.0 – 20.0 x ULN) ALT elevations were observed in 1% and 0% of TARCEVA and placebo treated patients, respectively. The TARCEVA treatment group had Grade 2 (>1.5-3.0 x ULN) bilirubin elevations in 4% and Grade 3 (>3.0-10.0 x ULN) in <1% compared with <1% for both Grades 2 and 3 in the placebo group. TARCEVA dosing should be interrupted or discontinued if changes in liver function are severe [see Dosage and Administration (2.3)].
Second/Third Line Study
Adverse reactions, regardless of causality, that occurred in at least 10% of patients treated with single- agent TARCEVA at 150 mg and at least 3% more often than in the placebo group in the randomized trial of patients with NSCLC are summarized by NCI-CTC (version 2.0) Grade in Table 2. The most common adverse reactions in this patient population were rash and diarrhea. Grade 3/4 rash and diarrhea occurred in 9% and 6%, respectively, in TARCEVA-treated patients. Rash and diarrhea each resulted in study discontinuation in 1% of TARCEVA-treated patients. Six percent and 1% of patients needed dose reduction for rash and diarrhea, respectively. The median time to onset of rash was 8 days, and the median time to onset of diarrhea was 12 days.
4
None
5
5.1
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
Pulmonary Toxicity
There have been reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving TARCEVA for treatment of NSCLC, pancreatic cancer or other advanced solid tumors. In the randomized single-agent NSCLC-studies [see Clinical Studies (14.1, 14.2)], the incidence of serious ILD-like events in the TARCEVA treated patients versus placebo treated patients was 0.7% versus 0% in the maintenance study and 0.8% for both groups in the 2nd and 3rd line study. In the pancreatic cancer study – in combination with gemcitabine – [see Clinical Studies (14.4)], the incidence of ILD-like events was 2.5% in the TARCEVA plus gemcitabine group vs. 0.4% in the placebo plus gemcitabine group. The overall incidence of ILD-like events in approximately 32,000 TARCEVA-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) was approximately 1.1%. Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome and lung infiltration. Symptoms started from 5 days to more than 9 months (median 39 days) after initiating TARCEVA therapy. In the lung cancer trials most of the cases were associated with confounding or contributing factors such as concomitant/prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections. In the event of an acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever, TARCEVA therapy should be interrupted pending diagnostic evaluation. If ILD is diagnosed, TARCEVA should be discontinued and appropriate treatment instituted as needed [see Dosage and Administration (2.3)].
5.2    Renal Failure
Cases of hepatorenal syndrome, acute renal failure (including fatalities), and renal insufficiency have been reported. Some were secondary to baseline hepatic impairment while others were associated with severe dehydration due to diarrhea, vomiting, and/or anorexia or concurrent chemotherapy use. In the event of dehydration, particularly in patients with contributing risk factors for renal failure (eg, pre-existing renal disease, medical conditions or medications that may lead to renal disease, or other predisposing conditions including advanced age), TARCEVA therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patient. Periodic monitoring of renal function and serum electrolytes is recommended in patients at risk of dehydration [see Adverse Reactions (6.1) and Dosage and Administration (2.3)].
5.3 Hepatotoxicity
Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported during use of TARCEVA, particularly in patients with baseline hepatic impairment. Therefore, periodic liver function testing (transaminases, bilirubin, and alkaline phosphatase) is recommended. In the setting of worsening liver function tests, dose interruption and/or dose reduction with frequent liver function test monitoring should be considered. TARCEVA dosing should be interrupted or discontinued if total bilirubin is >3 x ULN and/or transaminases are >5 x ULN in the setting of normal pretreatment values [see Adverse Reactions (6.1, 6.2) and Dosage and Administration (2.3)].
5.4    Patients with Hepatic Impairment
In a pharmacokinetic study in patients with moderate hepatic impairment (Child-Pugh B) associated with significant liver tumor burden, 10 out of 15 patients died on treatment or within 30 days of the last TARCEVA dose. One patient died from hepatorenal syndrome, 1 patient died from rapidly progressing liver failure and the remaining 8 patients died from progressive disease. Six out of the 10 patients who died had baseline total bilirubin > 3 x ULN suggesting severe hepatic impairment. Treatment with TARCEVA should be used with extra caution in patients with total bilirubin > 3 x ULN. Patients with hepatic impairment (total bilirubin > ULN or Child-Pugh A, B and C) should be closely monitored during therapy with TARCEVA. TARCEVA dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range [see Clinical Pharmacology (12.3) and Dosage and Administration (2.3)].
5.5    Gastrointestinal Perforation
Gastrointestinal perforation (including fatalities) have been reported in patients receiving TARCEVA. Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease are at increased risk. [see Adverse Reactions (6.1, 6.2)]. Permanently discontinue TARCEVA in patients who develop gastrointestinal perforation.
5.6    Bullous and Exfoliative Skin Disorders
Bullous, blistering and exfoliative skin conditions have been reported including cases suggestive of Stevens-Johnson syndrome/Toxic epidermal necrolysis, which in some cases were fatal [see Adverse Reactions (6.1, 6.2)]. Interrupt or discontinue TARCEVA treatment if the patient develops severe bullous, blistering or exfoliating conditions.
5.7    Myocardial Infarction/Ischemia
In the pancreatic carcinoma trial, six patients (incidence of 2.3%) in the TARCEVA/gemcitabine group developed myocardial infarction/ischemia. One of these patients died due to myocardial infarction. In comparison, 3 patients in the placebo/gemcitabine group developed myocardial infarction (incidence 1.2%) and one died due to myocardial infarction.

 7    DRUG INTERACTIONS
Erlotinib is metabolized predominantly by CYP3A4, and inhibitors of CYP3A4 would be expected to increase exposure. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased erlotinib AUC by 2/3. When TARCEVA was co-administered with ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17% respectively. Caution should be used when administering or taking TARCEVA with ketoconazole and other strong CYP3A4 inhibitors such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole and grapefruit or grapefruit juice [see Dosage and Administration (2.3)].
Pre-treatment with the CYP3A4 inducer rifampicin for 7 days prior to TARCEVA decreased erlotinib AUC by about 2/3 to 4/5, which is equivalent to a dose of about 30 to 50 mg in NSCLC patients. In a separate study, treatment with rifampicin for 11 days, with co-administration of a single 450 mg dose of TARCEVA on day 8 resulted in a mean erlotinib exposure (AUC) that was 57.6% of that observed following a single 150 mg TARCEVA dose in the absence of rifampicin treatment [see Dose Modifications (2.3)]. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, adjusting the starting dose should be considered. If the TARCEVA dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John’s Wort [see Dosage and Administration (2.3)].
Cigarette smoking has been shown to reduce erlotinib AUC. Patients should be advised to stop smoking; however, if they continue to smoke, a cautious increase in the dose of TARCEVA may be considered, while monitoring the patient’s safety. If the TARCEVA dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
Pretreatment and co-administration of TARCEVA decreased the AUC of CYP3A4 substrate, midazolam, by 24%. The mechanism is not clear. In a study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.
Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. Increasing the dose of TARCEVA when co-administered with such agents is not likely to compensate for the loss of exposure. Co-administration of TARCEVA with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with TARCEVA should be avoided if possible. Co-administration of TARCEVA with 300 mg ranitidine, an H2 receptor antagonist, decreased erlotinib AUC by 33%. When TARCEVA was administered with ranitidine 150 mg twice daily (at least 10 h after the previous ranitidine evening dose and 2 h before the ranitidine morning dose), the erlotinib AUC decreased by 15%. If patients need to be treated with an H2-receptor antagonist such as ranitidine, it should be used in a staggered manner. TARCEVA must be taken once a day, 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of H2-receptor antagonist. Although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the TARCEVA dose should be separated by several hours, if an antacid is necessary. [see Clinical Pharmacology (12.3)].

To read more please visit http://www.tarceva.com/pro_pancreatic/index.jsp. Your going to see that when you do research for this drug that it is for lung,breast,pancreatic and a few other cancers.  It is in trail stages for the Brain and hopefully will find a way to help others that are in my dads position.  If more studies are done maybe there will be away for future generations to find some sort of cure for this common and devastating cancer.  I know everyone is big on breast cancer and prostate but Brain cancer needs to be looked at more closely to. With out our brains we don't exist. 

Sites for research:

 http://www.cancer.org/cancer/braincnstumorsinadults/index?gclid=CNXf2uWeiq8CFUmc7QodL2DcAA

 http://www.milesforhope.org/

 http://www.braintumorfoundation.org/

I will be posting as time goes on about this topic. I will also try and answer any questions you all may have or help you into the right direction.

xoxo

New Kidney Cancer Med!

FDA NEWS RELEASE
For Immediate Release: Jan. 27, 2012
Media Inquiries: Stephanie Yao, 301-796-0394, stephanie.yao@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves Inlyta to treat patients with a type of advanced kidney cancer
Drug helps keep cancer from progressing

The U.S. Food and Drug Administration today approved Inlyta (axitinib) to treat patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer.
Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression. Inlyta is a pill that patients take twice a day.
“This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Collectively, this unprecedented level of drug development within this time period has significantly altered the treatment paradigm of metastatic kidney cancer, and offers patients multiple treatment options.”
Recently approved drugs for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009) and pazopanib (2009).
The safety and effectiveness of Inlyta were evaluated in a single randomized, open-label, multi-center clinical study of 723 patients whose disease had progressed on or after treatment with one prior systemic therapy. The study was designed to measure progression-free survival, the time a patient lived without the cancer progressing. Results showed a median progression-free survival of 6.7 months compared to 4.7 months with a standard treatment (sorafenib).
The most common side effects observed in greater than 20 percent of patients in the clinical study were diarrhea, high blood pressure (hypertension), fatigue, decreased appetite, nausea, loss of voice (dysphonia), hand-foot syndrome (palmar-plantar erythrodysesthesia), weight loss, vomiting, weakness (asthenia) and constipation.
Patients with high blood pressure should have it well-controlled before taking Inlyta. Some patients who took Inlyta experienced bleeding problems, which in some cases were fatal. Patients with untreated brain tumors or gastrointestinal bleeding should not take Inlyta.
Inlyta is marketed by New York City-based Pfizer Inc.

INLYTA® (in-ly-ta) (axitinib) Tablets
Read this Patient Information before you start taking INLYTA and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
What is INLYTA?
INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked.
It is not known if INLYTA is safe or effective in children.
What should I tell my doctor before taking INLYTA?
Before you take INLYTA, tell your doctor if you:
• have high blood pressure
• have thyroid problems
• have liver problems
• have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision
For females, tell your doctor if you:
• have any bleeding problems
• have an unhealed wound
• plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery.
• have any other medical conditions
• are pregnant or plan to become pregnant. Taking INLYTA during pregnancy may cause the death of an unborn baby or birth defects. You should not become pregnant while taking INLYTA. Talk to your doctor if you are pregnant or plan to become pregnant.
• are able to become pregnant. You should use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods to prevent pregnancy while you are taking INLYTA.
• are breastfeeding or plan to breastfeed. It is not known if INLYTA passes into your breast milk. You and your doctor should decide if you will take INLYTA or breastfeed. You should not do both.
For males:
• use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods.
• if your female partner becomes pregnant while you are taking INLYTA, tell your doctor right away.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. INLYTA and certain other medicines can affect each other causing serious side effects.
Especially tell your doctor if you take:
• dexamethasone
• St. John’s Wort (Hypericum perforatum)
• Medicine for:
• asthma
• tuberculosis
• seizures
• bacterial infections
• fungal infections • depression
• HIV or AIDS
Ask your doctor or pharmacist if you are not sure if your medicine is one listed above. If you are taking any medicines for the conditions listed above, your doctor might need to prescribe a different medicine or your dose of INLYTA may need to be changed. Talk with your doctor before you start taking any new medicine.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take INLYTA?
• Take INLYTA exactly as prescribed by your doctor.
• Your doctor may change your dose if needed.
• INLYTA can be taken with or without food.
• Take INLYTA 2 times a day approximately 12 hours apart.
• Swallow INLYTA tablets whole with a glass of water.
• Your doctor should check your blood pressure regularly during treatment with INLYTA.
• If you vomit or miss a dose of INLYTA, take your next dose at your regular time. Do not take two doses at
the same time.
• If you take too much INLYTA, call your doctor or go to the nearest hospital emergency room right away.
What should I avoid while taking INLYTA?
• Do not drink grapefruit juice or eat grapefruit. Grapefruit may increase the amount of INLYTA in your blood.
What are the possible side effects of INLYTA?
INLYTA may cause serious side effects, including:
• High blood pressure (hypertension). Your doctor should check your blood pressure regularly during treatment with INLYTA. If you develop blood pressure problems, your doctor may prescribe medicine to treat your high blood pressure, lower your dose, or stop your treatment with INLYTA.

• Thyroid gland problems. Your doctor should do blood tests to check your thyroid gland function before and during your treatment with INLYTA. Tell your doctor if you have any of the following symptoms during your treatment with INLYTA:
• tiredness that worsens or • weight gain or weight loss
that does not go away
• feeling hot or cold
• your voice deepens
• hair loss
• muscle cramps and aches
• Problem with blood clots in your veins or arteries. Get emergency help and call your doctor if you get any of the following symptoms:
• chest pain or pressure
• pain in your arms, back, neck or jaw
• shortness of breath
• numbness or weakness on one side of your body
• trouble talking • headache
• vision changes
• Bleeding. INLYTA can cause bleeding which can be serious, and sometimes lead to death. Call your doctor or get medical help if you develop any bleeding, including:
• unexpected bleeding or bleeding that lasts a long time, such as:
— unusual bleeding from the gums
— menstrual bleeding or vaginal bleeding that is
heavier than normal
— bleeding that is severe or you cannot control
— pink or brown urine
— red or black stools (looks like tar)
— bruises that happen without a known cause or get larger
— cough up blood or blood clots
— vomit blood or your vomit looks like
“coffee grounds”
— unexpected pain, swelling, or joint pain — headaches, feeling dizzy or weak
• Tear in your stomach or intestinal wall (perforation). Get medical help right away if you get the following symptoms:
• severe stomach (abdominal) pain or • vomit blood
stomach pain that does not go away
• red or black stools
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A condition called reversible posterior leukoencephalopathy syndrome (RPLS) can happen while taking INLYTA. Call you doctor right away if you get:
• headache • seizures
• weakness • confusion
• high blood pressure
• blindness or change in vision • problems thinking

• Increased protein in your urine. Your doctor should check your urine for protein before and during your treatment with INLYTA. If you develop protein in your urine, your doctor may decrease your dose of INLYTA or stop your treatment.
• Change in liver function. Your doctor should do blood tests before and during your treatment with INLYTA to check your liver function.
The most common side effects of INLYTA include: • diarrhea (frequent or loose bowel movements)
• high blood pressure
• tiredness or feeling weak • decreased appetite
• nausea
• hoarseness
• rash, redness, itching or peeling of your skin on your hands and feet
• decreased weight • vomiting
• constipation
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of INLYTA. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store INLYTA?
• Store INLYTA at room temperature between 68oF to 77oF (20oC to 25oC). Keep INLYTA and all medicines out of the reach of children.

FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE
INLYTA is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.
2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing
The recommended starting oral dose of INLYTA is 5 mg twice daily. Administer INLYTA doses approximately 12 hours apart with or without food [see Clinical Pharmacology (12.3)]. INLYTA should be swallowed whole with a glass of water.
If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.
2.2 Dose Modification Guidelines
Dose increase or reduction is recommended based on individual safety and tolerability.
Over the course of treatment, patients who tolerate INLYTA for at least two consecutive weeks with no adverse reactions >Grade 2 (according to the Common Toxicity Criteria for Adverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, the INLYTA dose may be increased to 7 mg twice daily, and further to 10 mg twice daily using the same criteria.
Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of INLYTA therapy [see Warnings and Precautions (5)]. If dose reduction from 5 mg twice daily is required, the recommended dose is 3 mg twice daily. If additional dose reduction is required, the recommended dose is 2 mg twice daily.
Strong CYP3A4/5 Inhibitors: The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of INLYTA by approximately half is recommended, as this dose reduction is predicted to adjust the axitinib area under the plasma concentration vs time curve (AUC) to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA dose should be returned (after 3 – 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Hepatic Impairment: No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmacokinetic data,
2

the INLYTA starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.11), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
1 mg tablets of INLYTA: red, film-coated, oval tablets, debossed with “Pfizer” on one side and “1 XNB” on the other side.
5 mg tablets of INLYTA: red, film-coated, triangular tablets, debossed with “Pfizer” on one side and “5 XNB” on the other side.
4 CONTRAINDICATIONS
None
5 WARNINGS AND PRECAUTIONS 5.1 Hypertension and Hypertensive Crisis
In a controlled clinical study with INLYTA for the treatment of patients with RCC, hypertension was reported in 145/359 patients (40%) receiving INLYTA and 103/355 patients (29%) receiving sorafenib. Grade 3/4 hypertension was observed in 56/359 patients (16%) receiving INLYTA and 39/355 patients (11%) receiving sorafenib. Hypertensive crisis was reported in 2/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. The median onset time for hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) was within the first month of the start of INLYTA treatment and blood pressure increases have been observed as early as 4 days after starting INLYTA. Hypertension was managed with standard antihypertensive therapy. Discontinuation of INLYTA treatment due to hypertension occurred in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)].
Blood pressure should be well-controlled prior to initiating INLYTA. Patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. In the case of persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. Discontinue INLYTA if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis. If INLYTA is interrupted, patients receiving antihypertensive medications should be monitored for hypotension [see Dosage and Administration (2.2)].
5.2 Arterial Thromboembolic Events
In clinical trials, arterial thromboembolic events have been reported, including deaths. In a controlled clinical study with INLYTA for the treatment of patients with RCC, Grade 3/4 arterial thromboembolic events were reported in 4/359 patients (1%) receiving INLYTA and 4/355 patients (1%) receiving sorafenib. Fatal cerebrovascular accident was reported in 1/359 patients

(<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)].
In clinical trials with INLYTA, arterial thromboembolic events (including transient ischemic attack, cerebrovascular accident, myocardial infarction, and retinal artery occlusion) were reported in 17/715 patients (2%), with two deaths secondary to cerebrovascular accident.
Use INLYTA with caution in patients who are at risk for, or who have a history of, these events. INLYTA has not been studied in patients who had an arterial thromboembolic event within the previous 12 months.
5.3 Venous Thromboembolic Events
In clinical trials, venous thromboembolic events have been reported, including deaths. In a controlled clinical study with INLYTA for the treatment of patients with RCC, venous thromboembolic events were reported in 11/359 patients (3%) receiving INLYTA and 2/355 patients (1%) receiving sorafenib. Grade 3/4 venous thromboembolic events were reported in 9/359 patients (3%) receiving INLYTA (including pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis) and 2/355 patients (1%) receiving sorafenib. Fatal pulmonary embolism was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. In clinical trials with INLYTA, venous thromboembolic events were reported in 22/715 patients (3%), with two deaths secondary to pulmonary embolism.
Use INLYTA with caution in patients who are at risk for, or who have a history of, these events. INLYTA has not been studied in patients who had a venous thromboembolic event within the previous 6 months.
5.4 Hemorrhage
In a controlled clinical study with INLYTA for the treatment of patients with RCC, hemorrhagic events were reported in 58/359 patients (16%) receiving INLYTA and 64/355 patients (18%) receiving sorafenib. Grade 3/4 hemorrhagic events were reported in 5/359 (1%) patients receiving INLYTA (including cerebral hemorrhage, hematuria, hemoptysis, lower gastrointestinal hemorrhage, and melena) and 11/355 (3%) patients receiving sorafenib. Fatal hemorrhage was reported in 1/359 patients (<1%) receiving INLYTA (gastric hemorrhage) and 3/355 patients (1%) receiving sorafenib.
INLYTA has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose.
5.5 GastrointestinalPerforationandFistulaFormation
In a controlled clinical study with INLYTA for the treatment of patients with RCC, gastrointestinal perforation was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. In clinical trials with INLYTA, gastrointestinal perforation was reported in 5/715 patients (1%), including one death. In addition to cases of gastrointestinal perforation, fistulas were reported in 4/715 patients (1%).
Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment with INLYTA.

5.6 Thyroid Dysfunction
In a controlled clinical study with INLYTA for the treatment of patients with RCC, hypothyroidism was reported in 69/359 patients (19%) receiving INLYTA and 29/355 patients (8%) receiving sorafenib. Hyperthyroidism was reported in 4/359 patients (1%) receiving INLYTA and 4/355 patients (1%) receiving sorafenib. In patients who had thyroid stimulating hormone (TSH) <5 μU/mL before treatment, elevations of TSH to ≥10 μU/mL occurred in 79/245 patients (32%) receiving INLYTA and 25/232 patients (11%) receiving sorafenib [see Adverse Reactions (6.1)].
Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state.
5.7 Wound Healing Complications
No formal studies of the effect of INLYTA on wound healing have been conducted.
Stop treatment with INLYTA at least 24 hours prior to scheduled surgery. The decision to resume INLYTA therapy after surgery should be based on clinical judgment of adequate wound healing.
5.8 Reversible Posterior Leukoencephalopathy Syndrome
In a controlled clinical study with INLYTA for the treatment of patients with RCC, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)]. There were two additional reports of RPLS in other clinical trials with INLYTA.
RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Discontinue INLYTA in patients developing RPLS. The safety of reinitiating INLYTA therapy in patients previously experiencing RPLS is not known.
5.9 Proteinuria
In a controlled clinical study with INLYTA for the treatment of patients with RCC, proteinuria was reported in 39/359 patients (11%) receiving INLYTA and 26/355 patients (7%) receiving sorafenib. Grade 3 proteinuria was reported in 11/359 patients (3%) receiving INLYTA and 6/355 patients (2%) receiving sorafenib [see Adverse Reactions (6.1)].
Monitoring for proteinuria before initiation of, and periodically throughout, treatment with INLYTA is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt INLYTA treatment.
5.10 Elevation of Liver Enzymes
In a controlled clinical study with INLYTA for the treatment of patients with RCC, alanine aminotransferase (ALT) elevations of all grades occurred in 22% of patients on both arms, with Grade 3/4 events in <1% of patients on the INLYTA arm and 2% of patients on the sorafenib arm.
Monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with INLYTA.
5
5.11 Hepatic Impairment
The systemic exposure to axitinib was higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with normal hepatic function. A dose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child- Pugh class B). INLYTA has not been studied in patients with severe hepatic impairment (Child- Pugh class C) [see Dosage and Administration (2.2), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
5.12 Pregnancy
INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women using INLYTA. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving INLYTA. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of INLYTA has been evaluated in 715 patients in monotherapy studies, which included 537 patients with advanced RCC. The data described [see Adverse Reactions (6.1)] reflect exposure to INLYTA in 359 patients with advanced RCC who participated in a randomized clinical study versus sorafenib [see Clinical Studies (14)].
The following risks, including appropriate action to be taken, are discussed in greater detail in other sections of the label [see Warnings and Precautions (5.1-5.10 and 5.12)]: hypertension, arterial thromboembolic events, venous thromboembolic events, hemorrhage, gastrointestinal perforation and fistula formation, thyroid dysfunction, wound healing complications, RPLS, proteinuria, elevation of liver enzymes, and fetal development.
6.1 Clinical Trials Experience
The median duration of treatment was 6.4 months (range 0.03 to 22.0) for patients who received INLYTA and 5.0 months (range 0.03 to 20.1) for patients who received sorafenib. Dose modifications or temporary delay of treatment due to an adverse reaction occurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in 34/359 patients (9%) receiving INLYTA and 46/355 patients (13%) receiving sorafenib.
The most common (≥20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea,erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. Table 1 presents adverse reactions reported in ≥10% patients who received INLYTA or sorafenib.

7 DRUG INTERACTIONS
In vitro data indicate that axitinib is metabolized primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.
7.1 CYP3A4/5 Inhibitors
Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5
8

inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor must be co- administered, the INLYTA dose should be reduced [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
7.2 CYP3A4/5 Inducers
Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John’s wort) should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 induction potential is recommended [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitinib and should be avoided if possible.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D [see Warnings and Precautions (5.12)].
There are no adequate and well-controlled studies with INLYTA in pregnant women. INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.
Oral axitinib administered twice daily to female mice prior to mating and through the first week of pregnancy caused an increase in post-implantation loss at all doses tested (≥15 mg/kg/dose, approximately 10 times the systemic exposure (AUC) in patients at the recommended starting dose). In an embryo-fetal developmental toxicity study, pregnant mice received oral doses of 0.15, 0.5 and 1.5 mg/kg/dose axitinib twice daily during the period of organogenesis. Embryo- fetal toxicities observed in the absence of maternal toxicity included malformation (cleft palate) at 1.5 mg/kg/dose (approximately 0.5 times the AUC in patients at the recommended starting dose) and variation in skeletal ossification at ≥0.5 mg/kg/dose (approximately 0.15 times the AUC in patients at the recommended starting dose).
8.3 NursingMothers
It is not known whether axitinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from INLYTA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and efficacy of INLYTA in pediatric patients have not been studied. 9

Toxicities in bone and teeth were observed in immature mice and dogs administered oral axitinib twice daily for 1 month or longer. Effects in bone consisted of thickened growth plates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, the systemic exposure (AUC) in patients at the recommended starting dose). Abnormalities in growing incisor teeth (including dental caries, malocclusions and broken and/or missing teeth) were observed in mice administered oral axitinib twice daily at ≥5 mg/kg/dose (approximately 1.5 times the AUC in patients at the recommended starting dose). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals.
8.5 Geriatric Use
In a controlled clinical study with INLYTA for the treatment of patients with RCC, 123/359 patients (34%) treated with INLYTA were ≥65 years of age. Although greater sensitivity in some older individuals cannot be ruled out, no overall differences were observed in the safety and effectiveness of INLYTA between patients who were ≥65 years of age and younger.
No dosage adjustment is required in elderly patients [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
8.6 Hepatic Impairment
In a dedicated hepatic impairment trial, compared to subjects with normal hepatic function, systemic exposure following a single dose of INLYTA was similar in subjects with baseline mild hepatic impairment (Child-Pugh class A) and higher in subjects with baseline moderate hepatic impairment (Child-Pugh class B).
No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). A starting dose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child-Pugh class B) [see Dosage and Administration (2.2), Warnings and Precautions (5.11), and Clinical Pharmacology (12.3)].
INLYTA has not been studied in subjects with severe hepatic impairment (Child-Pugh class C).
8.7 Renal Impairment
No dedicated renal impairment trial for axitinib has been conducted. Based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 mL/min ≤creatinine clearance [CLcr] <89 mL/min) [see Clinical Pharmacology (12.3)]. No starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. Caution should be used in patients with end- stage renal disease (CLcr <15 mL/min).
10 OVERDOSAGE
There is no specific treatment for INLYTA overdose.
In a controlled clinical study with INLYTA for the treatment of patients with RCC, 1 patient inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action
Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.
12.2 Pharmacodynamics
The effect of a single oral dose of INLYTA (5 mg) in the absence and presence of 400 mg ketoconazole on the QTc interval was evaluated in a randomized, single-blinded, two-way crossover study in 35 healthy subjects. No large changes in mean QTc interval (i.e., >20 ms) from
11
placebo were detected up to 3 hours post-dose. However, small increases in mean QTc interval (i.e., <10 ms) cannot be ruled out.
12.3 Pharmacokinetics
The population pharmacokinetic analysis pooled data from 17 trials in healthy subjects and patients with cancer. A two-compartment disposition model with first-order absorption and lag- time adequately describes the axitinib concentration-time profile.
Absorption and Distribution: Following single oral 5-mg dose administration, the median Tmax ranged from 2.5 to 4.1 hours. Based on the plasma half-life, steady state is expected within 2 to 3 days of dosing. Dosing of axitinib at 5 mg twice daily resulted in approximately 1.4-fold accumulation compared to administration of a single dose. At steady state, axitinib exhibits approximately linear pharmacokinetics within the 1-mg to 20-mg dose range. The mean absolute bioavailability of axitinib after an oral 5 mg dose is 58%.
Compared to overnight fasting, administration of INLYTA with a moderate fat meal resulted in 10% lower AUC and a high fat, high-calorie meal resulted in 19% higher AUC. INLYTA can be administered with or without food [see Dosage and Administration (2.1)].
Axitinib is highly bound (>99%) to human plasma proteins with preferential binding to albumin and moderate binding to α1-acid glycoprotein. In patients with advanced RCC (n=20), at the 5 mg twice daily dose in the fed state, the geometric mean (CV%) Cmax and AUC0-24 were 27.8 (79%) ng/mL and 265 (77%) ng.h/mL, respectively. The geometric mean (CV%) clearance and apparent volume of distribution were 38 (80%) L/h and 160 (105%) L, respectively.
Metabolism and Elimination: The plasma half life of INLYTA ranges from 2.5 to 6.1 hours. Axitinib is metabolized primarily in the liver by CYP3A4/5 and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Following oral administration of a 5-mg radioactive dose of axitinib, approximately 41% of the radioactivity was recovered in feces and approximately 23% was recovered in urine. Unchanged axitinib, accounting for 12% of the dose, was the major component identified in feces. Unchanged axitinib was not detected in urine; the carboxylic acid and sulfoxide metabolites accounted for the majority of radioactivity in urine. In plasma, the N- glucuronide metabolite represented the predominant radioactive component (50% of circulating radioactivity) and unchanged axitinib and the sulfoxide metabolite each accounted for approximately 20% of the circulating radioactivity.
The sulfoxide and N-glucuronide metabolites show approximately ≥400-fold less in vitro potency against VEGFR-2 compared to axitinib.
Drug-Drug Interactions
Effects of Other Drugs on INLYTA: Axitinib is metabolized primarily in the liver by CYP3A4/5. Additionally, the aqueous solubility of axitinib is pH dependent, with higher pH resulting in lower solubility. The effects of a strong CYP3A4/5 inhibitor, a strong CYP3A4/5 inducer, and an antacid on the pharmacokinetics of axitinib are presented in Figure 1 [see Dosage and Administration (2.2) and Drug Interactions (7.1, 7.2)].



For complete information go to Pfizer's web site. I included as much as I could here. :)

New drug that helps skin cancer

Genentech Drug Shrinks Advanced Basal Cell Cancers
By Daniel J. DeNoon
Reviewed by Laura J. Martin, MD
WebMD Health News

Jan. 31, 2012 -- The FDA has approved Erivedge, a once-daily pill that can shrink disfiguring or metastatic basal cell carcinoma (BCC) tumors.

BCC, the most common form of skin cancer, usually is curable. But in rare cases, the cancer spreads through the body or invades surrounding parts of the body.

These advanced, sometimes disfiguring cancers often cannot be completely eliminated with surgery or radiation.

But BCC cancer cells need a signal, dubbed Hedgehog, to grow. Erivedge inhibits this signal.

In a single clinical study that enrolled 96 patients with advanced or spreading BCC, Erivedge shrank the tumors in 30% of those with metastatic cancer and shrank or eliminated tumors in 43% of patients with locally advanced cancer.

That was enough for the FDA to approve Erivedge under its speediest form of review.

The approval comes with the FDA's "black box" warning -- it's most severe safety alert -- noting that the drug carries a risk of causing stillbirth or severe birth defects. It cannot be used by pregnant women. Men taking Erivedge must use condoms, even if they have had vasectomies, to avoid unintentionally contaminating their female partners with the drug.

The most common side effects observed in patients treated with Erivedge were muscle spasms, hair loss, weight loss, nausea, diarrhea, fatigue, distorted sense of taste, decreased appetite, constipation, vomiting, and loss of taste function in the tongue.

Erivedge will be available in the U.S. within two weeks. However, it will not be sold at retail pharmacies, but must be dispensed at "specialty pharmacies" where staff is trained to offer patient education.

Erivedge is made by Genentech, a Roche company. The firm says it soon will seek approval in the European Union.
Recommended dose of ERIVEDGE is 150 mg taken orally once daily until disease progression or until unacceptable toxicity.
ERIVEDGE may be taken with or without food. Swallow capsules whole. Do not open or crush capsules.

If a dose of ERIVEDGE is missed, do not make up that dose; resume dosing with the next scheduled dose.

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Erivedge:

Constipation; diarrhea; hair loss; joint pain; loss of appetite; loss of taste or other taste changes; muscle spasms; nausea; tiredness; vomiting; weight loss.

Seek medical attention right away if any of these SEVERE side effects occur when using Erivedge:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); absent menstrual period; decreased urination; symptoms of low blood potassium levels (eg, muscle pain, weakness, or cramping; irregular heartbeat); symptoms of low blood sodium levels (eg, confusion, mental or mood changes, seizures, sluggishness).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Lucid Dreaming

This is a topic that is very interesting to me. It can be done. Enjoy. Xoxo


Lucid dreaming is awareness of the fact that you are dreaming. This awareness can range from very faint recognition of the fact (which is often too brief and nebulous to be considered truly lucid) to something as momentous as a broadening of awareness beyond what has ever been experienced even in waking life. What a dreamer does with lucidity reflects personal tendencies and levels of skill attained usually through experience and practice. Although a lucid dreamer can influence the dream's structure, characters, course, etc., it is not a given that a lucid dream is about what the dreamer wants it to be about. Seasoned lucid dreamers who are more often lucid than not will continue to encounter psychological and developmental challenges in the dreamscape. The agreeable and the distressing, the easy and difficult, beautiful and horrifying, are all occasioned much as they are in regular dreaming. But whereas a regular dream is filled with the convoluted subtleties of the subconscious mind enumerating its issues before a largely unconscious dreamer, a lucid dreamer has the opportunity to consciously explore at any level. Lucid dreams usually occur while a person is in the middle of a regular dream and suddenly realizes that he or she is dreaming. The person is then said to be "lucid", and may enter one of many levels of lucidity. At the lowest level, the dreamer may be dimly aware that he or she is dreaming, but not think rationally enough to realize that events/people/actions in the dream are not real/pose no threat. At the highest level, the dreamer is fully aware that she or he is asleep, and can have complete control over his or her actions in the dream. However, with low mental control your decisions could be biased not by your opinion, but by your brain. You can control your dreams using the lucid dreaming methods that follow.
1During the day, repeatedly ask "Am I dreaming?" and perform some reality checks whenever you remember. With practice, if it happens enough, you will automatically remember it during your dreams and do it.
2Keep a dream journal. This is perhaps the most important step towards lucid dreaming. Keep it close by your bed at night, and write in it immediately after waking. Or you can keep a recording device if you find it easier to repeat your dream out loud. This helps you recognize your common dream elements (people from your past, specific places, etc.), and also tells your brain that you are serious about remembering your dreams! It will also help you to recognize things that are unique to your dreams. You will be able to recognize your own "dream signs." These will be recurring things or events that you may notice in your dreams.
3Learn the best time to have a lucid dream. By being aware of your personal sleep schedule, you can arrange your sleep pattern to help induce lucid dreams.

Studies strongly suggest that a nap a few hours after waking in the morning is the most common time to have a lucid dream.
Lucid dreams are strongly associated with REM sleep. REM sleep is more abundant just before the final awakening. This means they most commonly occur right before waking up. (Sleep-onset REM is a symptom of narcolepsy. If you have lucid dreams right after falling asleep, you may wish to consider seeking medical advice from a sleep medicine specialist. However, there are studies which show people can recall dreams after being awakened during non-REM sleep).
Dreams usually run in 60-minute (Weiten Psych book 2004) cycles during sleep. If you are working on dream recall, it may be helpful to try waking yourself up during one of these cycles (interrupted dreams are often the ones we remember).
4Try Stephen Laberge's mnemonic induction of lucid dreaming (MILD) technique.

Set your alarm clock to wake you up 4 1/2, 6, or 7 1/2 hours after falling asleep.
When you are awakened by your alarm clock, try to remember the dream as much as possible.
When you think you have remembered as much as you can, return to your place of rest, imagining that you are in your previous dream, and becoming aware that you are dreaming. Say to yourself, "I will be aware that I'm dreaming," or something similar. Do this until you think that it has "sunk in." Then go to sleep.
If random thoughts pop up when you are trying to fall asleep, repeat the imagining, self-suggestion part, and try again. Don't worry if you think it's taking a long time. The longer it takes, the more likely it will 'sink in,' and the more likely you will have a lucid dream.
5Attempt the WBTB (Wake Back To Bed) Technique. This is the most successful technique.
Set your alarm clock to 5 hours after you fall asleep.
Fall asleep.
After you wake up, stay up for an hour with your mind focused on lucidity and lucidity only.
Go back to sleep using the MILD technique.
6Try attempting the WILD (wake initiated lucid dream) technique. Basically what it means is that when you fall asleep you carry your awareness from when you were awake directly into REM sleep and you start out as a lucid dream.

The easiest way to attempt this technique is if you take an afternoon nap or you have only slept for 3-7 hours.
Try to meditate into a calm but focused state. You can try counting breaths, imaging ascending/descending stairs, dropping through the solar system, being in a quiet soundproof area, etc.
Listening to Theta binaural beats for an amount time will easily put you into a REM sleep.
See the warnings at the bottom, as these are very important.
7Another technique for overall "dream awareness" is the Diamond Method of meditation, which can shortcut the overall learning curve, of Lucid Dreaming.

When one meditates, try to visualize your life, both awake and dream-life as facets on a diamond. Some choose to call this "diamond" the Universe, others God, and even "your Spirit." The point here is to begin to recognize that life is happening all at once. It is only our "Perception" that arranges our dramas into linear or "timed" order. So just as a diamond just is, each facet if viewed as an individual experience, still is going on at the same time the "Dream Body" experiences as well. This method is also known by Remote Viewers. Remember it is just a slight shift in awareness that this exercise calls for.
8Immerse yourself in the subject of lucid dreaming. For example, you can look on lucid dreaming websites, watch movies with lucid dreaming (eg. Waking Life, Vanilla sky, Inception), read books about it, etc...
9Try marking an "A" (which stands for "awake") on your palm. Every time you notice the "A" during your waking hours challenge whether you are awake or asleep. Eventually you may see the "A" in your sleep and become lucid.
10

Get into the habit of doing reality checks. Do at least three reality checks every time something seems out of the ordinary, strongly frustrating, or nonsensical, and that habit will carry on into your dreams. In a dream, these will tell you that you are sleeping, allowing you to become lucid. In order to remember to do reality checks in dreams, you need to establish a habit of doing reality checks in real life. One way to do a reality check is to look for "dream signs" (elements that frequently occur during your dreams, look for these in your dream journal), or things that would not normally exist in real life, and then conduct the reality checks. When these actions become habit, a person will begin to do them in her or his dreams, and can come to the conclusion that he/she is dreaming. Frequently doing reality checks can stabilize dreams. This is also known as DILD (Dream Induced Lucid Dreams). Some tactics include:
Looking at a digital clock to see if it stays constant;
Looking at a body of text, looking away, and then looking back to see if it has changed;
Flipping a light switch;
Looking in a mirror (your image will most often appear blurry or not appear at all in a dream). However, your figure can be horribly disfigured in a mirror, frightening you into nightmare or a dream.
Pinching your nose closed and trying to breathe;
Glancing at your hands, and asking yourself, "am I dreaming?" (when dreaming, you will most often see greater or fewer than five fingers on your hand);
Jumping in the air; you are usually able to fly during dreams
Poking yourself; when dreaming, your "flesh" might be more elastic than in real life; a common reality check is pushing your finger through the palm of your hand;
Try leaning against a wall. In dreams, you will often fall through walls.
11Prolong lucid dreams by spinning your body or falling backwards in the dream (suspected of prolonging REM), and rubbing your hands (prevents you from feeling the sensation of lying in bed). Take care while spinning. Remind yourself even as you spin or fall that you are dreaming, as you will find yourself in a completely different location when you stop spinning or hit the ground and may lose lucidity otherwise. If you feel a dream 'shakes' or is about to fade out, look down to the ground and visualize your surroundings, reminding yourself you are dreaming.
12Be Pro-active about your dream. Have a goal in mind and try to accomplish it.
13Listen to Binaural Beats. Binaural Beats are often used to induce lucid dreams, and many assure this method dramatically improves success rate. Theoretically, listening to Binaural Beats lowers brain frequencies, triggering different effects such as relaxation and dream induction. Look for Theta bin-aural beats, as they use the same brainwave frequency used in dreams. You may also want to listen to Alpha and Delta binaural beats as they help you relax and fall into non-REM sleep.
14Look through previous dreams in your Dream Journal. If you start to notice patterns in your dreams, you will notice dream-signs, or certain things that continue to reappear in your dreams. This may be as basic as all dreams are in your backyard, or all your dreams have fans in them. Get into the habit of doing dream checks every time you see your dream sign, and eventually you'll see your dream sign IN a dream, do a check and realize you're dreaming.
Modified Look at Hand Method

A Modified Version of Gritz's "Looking At Your Hands"
1As you prepare for sleep each night, sit in your bed and take a minute to relax. look at the palms of your hands for 30 minutes, and repeat to yourself, "I will dream about", "your own dream."
2Continue to repeat this phrase, "I will dream about", "your own dream" as you look at your hands.
3After the thirty minutes, or whenever you get tired turn off the light and go to sleep.
4When you wake during the night, Look at your hand, and say the same phrase. If you did not see your hands, remind yourself of your intent to see your hands in the next dream.
5With consistent practice of this phrase each night before sleep, you will suddenly see your hands pop up in front of you when dreaming, and consciously realize, "My hands!" Oh my gosh! This is a dream.

There can be special cues to lucid dreams to find. For example, you may find colors or walls shifting and changing in unnatural ways, try to pick up these changes and you may realize you are lucid dreaming.
Lucid dreaming may be helpful for people who frequently experience nightmares, as it gives them a chance to take control of their dreams.
It is fun to fly in lucid dreams. To start flying try bouncing higher and higher after each step (while "walking" in the dream.) Some find that they need to train themselves, while others can just think that they want to fly, and therefore lift off the ground, and start to hover. You can also try walking on walls or the ceiling, as flying for the first time can be intimidating if you are not totally convinced that you are dreaming. Many people experience flying as being very natural and very exhilarating.
It is also cool to teleport. Close your eyes, spin your dream body, and envision a brand new landscape and open your eyes.
You can also try shape-shifting. It is hard to do it on command, but you can also make an 'excuse' to transform by making a transformation machine or a magic assistant that can change you into an animal.
These aren't the only things you can do. You can create anything you want, be whatever you want, do whatever you want. Of course, you need experience in lucid dreaming, or else it will be more difficult to dream.
Performing reality checks upon awakening can help you to detect "false awakenings" within dreams, wherein you dream that you have woken up, and thus lose lucidity.
If you want to dream about something or someone specifically, as you slip into a light sleep, think about that person or that object. The way it feels, the way it looks, the way it smells, etc.. This will cause your mind to focus on that object or person and chances are your dream will reflect upon it.
If you have recurring dreams, then aspects of these dreams can act as reality checks. If you notice something happening that is part of a recurring dream, think to yourself, "this only happens in my dreams, I must be dreaming."
If you notice something happening that is impossible in real life, such as being able to breathe underwater, this can act as a reality check to alert you to the fact that you are dreaming.
If you ask people in your dream "Am I dreaming?"... most of the time they'll say "No."
When recalling a dream upon waking, try not to move. Activating your muscle neurons can make it more difficult to access the parts of your brain that allow you to recall your dream.
If you cannot remember the dream, focus on the feelings that you felt. Trying too hard to remember the dream will only take your mind away from it. Chances are your mind will think of everything but the dream.
When you wake up naturally - that is, without an alarm - focus your gaze on the first object you see as you open your eyes. Look at the object; focus on it. That object will most often take the vague recollection of your dream to a place mark in memory where it is easier to recall details. A doorknob, a light bulb, a set of car keys, or a nail in the wall, for example, will quell your urge to begin your day, and will help you to settle into memories of what you had experienced while sleeping.
Do not use a radio alarm clock. If you hear talking or a song, it will distract you and may clear the dream out of your head. If you have to use a radio alarm clock, don't think about what is playing and quickly turn it off. Alternatively, change the radio setting to a non-assigned frequency so the alarm creates static (white noise).
To end sleep paralysis (which is not dangerous) try wiggling your toes or swallowing. When you are in sleep paralysis, your brain is sending a signal to the rest of your body to immobilize your muscles so you don't thrash around while you sleep. The larger muscles are usually more affected than the smaller ones. So trying to wiggle your toes tends to wake you up during a state of sleep paralysis.
Pre-determine what you want to achieve in a lucid dream while you are awake. When you become lucid in a dream, you will already know what you want to do.
It is a good idea to purposely wake a few minutes after becoming lucid, once you have experienced what you wanted to experience. This way, you can wake up with the dream very fresh in your mind, and have excellent recall. If you do not wake up, the dream may simply fade away into the night, and could be forgotten.
Some people find it helpful to take a low dose of caffeine (a caffeinated tea, for instance) shortly before sleeping. They claim that this keeps them mentally aware while the body is going to sleep. For other people caffeine may postpone or disrupt sleep.
Do not drink any fluids for one hour prior to sleeping. The last thing you want is to wake up from successfully lucid dreaming just because you had to use the bathroom.
As you get older, it will be harder to lucid dream, and it starts getting difficult during the teenage years of puberty.
Before you go to sleep, think really hard about getting up without actually doing so. You will be able to lucid dream at the beginning of your dream.
If you find the dream is not going how you want it to, "close your eyes" for a bit and then open very forcefully. It might not work the first time but you will eventually end up actually opening them.
Be careful about looking in mirrors - it can often help you determine that you are asleep, but be prepared to see how you feel about yourself.
Try not to worry about what might happen in the dream. Try to remember it's only a dream, and nothing there can hurt you. If you worry a lot about the people in your dream attacking you, for example, quite likely they will.
Write down what you remember when you remember it. Most people remember dreams from nights before If you write down whatever you remember, your brain will get used to remembering instances from your dreams.
When you are aware you are dreaming, make sure you know it is a dream at all times. Remember, there are no social consequences, everything, even the characters are just part of your imagination, you cannot get hurt, you need make to keep your dream stable, and you have total control of everything, including your actions, other characters actions, the environment, even physics with a few thoughts. Remember that and you will have total control over dreams at all times.
You can try visualizing something in your hand, or in your pocket. Trying to feel its weight, shape, and texture may help. In case of a nightmare, or other frightening dream, if practiced, this can become a self-defense system against any of those perils. Of course, they will not really harm you, but it IS fun to blast a horribly disfigured monster at point-blank with a rocket-launcher of some sort...
Supplements

Galantamine used with Choline bitartrate or Alpha-GPC can dramatically increase your odds of becoming Lucid.
An Amino Acid Blend made up of 2000mg L-aspartic acid, 4000mg L-glutamine, and 300mg L-theanine can substantially increase your odds of having a Lucid Dream.
5-HTP is the immediate precursor of serotonin, and can increase your odds of having a Lucid Dream greatly.
Vitamin B6 can increase dream vividness. (Bananas, Most fish)
Fish Oil helps recall dreams.
Ginko Biloba may have a similar effect to B6.
Melatonin makes dreams seem extremely vivid and usually only on one subject.

Please note that attempting WILD has a very small chance of causing you to suffer from sleep paralysis, rapid vibrations and noises that don't really exist, floating and other out-of-body experiences, and hypnagogic hallucinations/images, and anxiety. There is no reason to be afraid, as Sleep Paralysis happens every night - you just sleep through it. Hypnagogia is just your mind being overactive. Remember that with lucid dreaming you are aware and can always wake yourself up if you feel overwhelmed.
Remember if you get very excited during your lucid dream, it might cause you to wake up suddenly. At this point, focus on your dream, rub your hands, or spin around and concentrate.
If you lucid dream, remember to make it a great experience, and do not be disappointed when you wake up.
Do not watch pornographic material before going to sleep, it will keep you from focusing on your dreams.