NEWS FROM THE FDA!

1.PEGINESATIDE A DRUG INDICATED FOR ANEMIA OF CHRONIC RENAL FAILURE HAS BEEN PULLED FROM THE MARKET BECAUSE OF 3 DEATHS FROM ANAPHYLACTIC SHOCK REPORTEDLY.

2.REGORAFENIB, APPROVED IN METASTATIC COLON CANCER, JUST GOT APPROVED BY THE FDA FOR REFRACTORY GIST TUMOR AFTER FAILURE OF GLEEVEC AND SUTENT.

"The most common adverse effects reported with regorafenib are weakness and fatigue, hand-foot syndrome, diarrhea, loss of appetite, high blood pressure, mouth sores, infection, changes in voice volume or quality, pain, weight loss, stomach pain, rash, fever, and nausea."

FROM MEDSCAPE:

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IN OTHER NEWS,

18 MONTHS  ANDROGEN DEPRIVATION WAS COMPARBLE TO 36 MONTHS FOR SURVIVAL AFTER 77 MONTHS OF OBSERVATION WITH ABOUT 25% OF PATIENTS DYING FROM LOCALLY ADVANCED POOR PROGNOSIS PROSTATE CANCER. WITH POOR PROGNOSIS DEFINED AS PSA>20 AND GLEASON>7 ACCORDING TO CANADIAN RESEARCHERS!

RENAL CANCER PREVENTION (CHRONIC USE OF DECONGESTANT -AFRIN- COULD DECREASE RENAL CANCER.) and so does a CPAP mask for patients with Sleep Apnea

Renal cell cancer risk is associated to smoking and Obesity (hypertension is a corollary risk we claim).   These 2 conditions lead to Hypoxia generally through sleep Apnea  which in turn leads to a relative increase of Hemoglobin. The rise of Hemoglobin increases the portion of Desaturated hemoglobin. After many years of such exposure desaturated Heme enhances Phosphorylation at Tyr-530 of the SRC leading to its deactivation. In some individuals with the right MEK, suppression pf the SRC could lead to persistent amplification at the MEK which is a versatile activator of almost all signals, but particularly VEGF receptor.  This in turn usually lead to papillary cancers. Amplification of signal transduction started at the MEK (which amplifies almost all major known pathways) will lead to increased ubiquitination and proteasome destruction of the HYPOXIA-inducible factor  (following the Von Hippel-Lindau model.  This will lead to clear cell cancer. Associated desaturated Heme and hypoxia at the mitochondria will participate in the transformation (and possibly the Atypia/clear cell transformation).  The preponderance and center piece role of MEK amplification and subsequent VGEF/PDGF will justify the "bloody" nature of kidney cancers, and vessel involvement in these diseases  (MEK is the driver Mutation in papillary cancers).  IT ALSO EXPLAINS WHY SUTENT, NEXAVAR WORKS.  AND MITOCHONDRIAL DISTURBANCES AND SECONDARY AMPLIFICATION OF AKT, THE MTOR INHIBITORS WORK IN RENAL CANCERS  (MTOR participates more in clear cells)  (proof of concept pending)

In Western society, obesity is increasing, and so is Sleep Apnea.  Also, we live in closed homes (in some regions such as Texas and Louisiana, Mosquitoes are not helping) the level of dust participates in the increased level of allergic Rhinitis/ upper respiratory ailments.  It is not unusual to sleep and wake with closed Nostrils.  In obese individuals, this compounds the hypoxic episodes and worsened and prolonged hypoxia.  And we are back to depression of SRC, activation of MEK---akt, MAPK and so forth.
Keeping your nostrils open at night appears to be a critical strategy in preventing renal cancer, particularly in patients with breathing issues.   Lung cancer may be reduced for non smokers, but I wont touch that speculation, but do remember the role of VEGF in non-smoker lung cancers!

The involvement of PDGF which is by the way affected by Sutent seems to open a window in the frequency of strokes and heart attacks at night!  That's another debate to have...!

MTOR inhibitor in combination with Anti-VGEF/ MEK could have a significant role in non smoker lung cancer.?
Velcade could have a role in VHL prevention ? and in Pheochromocytoma?

Avastin and Mtor inhibitor could treat Leiomysarcoma of the Uterus if you follow this logic!

A FREED CPRIT AND THE NIH COULD HELP!

SUTENT FOR METASTATIC RENAL CELL CANCER!     

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	Dear Dr. Kankonde, Come explore patient support strategies, patient management, and other relevant issues. Discover for yourself how SUTENT may be appropriate for your mRCC patients.
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	SUTENT is indicated for the treatment of advanced renal cell carcinoma (RCC). Important Safety Information Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant. Cardiovascular events, including heart failure, myocardial disorders, and cardiomyopathy, some of which were fatal, have been reported through post-marketing experience. Monitor patients for signs and symptoms of congestive heart failure (CHF) and, in the presence of clinical manifestations, discontinuation is recommended. Patients who presented with cardiac events, pulmonary embolism, or cerebrovascular events within the previous 12 months were excluded from clinical studies. SUTENT has been shown to prolong QT interval in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias including torsades de pointes, which has been seen in <0.1% of="" patients.="" monitoring="" with="" on-treatment="" electrocardiograms="" and="" electrolytes="" should="" be="" considered.=""></0.1%>