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Pharmaceutical Approval Update: Oncology Sorafenib Tosylate (Nexavar)

Manufacturer: Bayer Health Care, West Haven, CT, and Onyx, Emeryville, CA

Indication: Sorafenib tablets are indicated for the treatment of advanced renal cell carcinoma.

Drug Class: As a multikinase inhibitor that targets a number of serine/threonine and receptor tyrosine kinases, sorafenib has the chemical name 4-(4-{3-[4-chloro-3-(tri-fluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide 4-methylbenzenesulfonate.

Uniqueness of Drug: Sorafenib possesses disruptive activity at intracellular CRAF, BRAF, and mutant BRAF receptors and at extracellular KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-p receptors. Inhibition of these systems blocks the division and growth of tumor cells and potentiates cellular apoptosis. These kinases are involved in multiple systems of angiogenesis and intracellular signaling, and their disruption is thought to inhibit tumor growth. kamagra uk

Warnings: In pregnant rats and rabbits, sorafenib is teratogenic and induces embryo and fetal toxicity, including increased post-implantation loss, resorption, skeletal retardation, and retarded fetal weight. The effects occurred at doses considerably below the recommended human dose of400 mg twice daily (about 500 mg/m2 per day on the basis of body surface area). Adverse intrauterine development effects were seen at doses of 1.2 mg/m2 per day or higher in rats and at doses of 3.6 mg/m2 per day in rabbits (about 0.008 times the AUC level seen in cancer patients at the recommended human dose).

Based on the proposed mechanism of multikinase inhibition and multiple adverse effects seen in animals at exposure levels significantly below the clinical dose, it is assumed that sorafenib causes fetal harm during pregnancy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.


Skin Reactions. Hand and foot reactions and rashes represent the most common adverse events attributed to sorafenib.
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Hypertension. In one study, treatment-emergent hypertension was reported in approximately 16.9% of sorafenib-treated patients and in 1.8% of patients in the placebo group. Hypertension was usually mild to moderate, occurring early in the course of treatment, and was managed with standard anti-hypertensive therapy.

Hemorrhage. An increased risk of bleeding may occur following sorafenib administration.

Cardiac Events. In one study, the incidence of treatment-emergent cardiac ischemia and infarction events was higher in the sorafenib group of patients (2.9%) compared with the placebo group (0.4%).

Dosage and Administration: Each oral sorafenib tablet contains 200 mg of the drug. The recommended dosage is 400 mg (two tablets) twice daily. As necessary, the dose may be reduced to 400 mg once daily or once every other day to manage treatment-related toxicity.

Commentary: Sorafenib is a targeted drug that is specifically engineered to inhibit RAF kinase within cancer cells. RAF, in turn, is part of the RAS, a gene that drives cell division and is overexpressed in many cancers, including renal cell carcinoma.

The key advantage of sorafenib is its ability to double the progression-free survival in patients with advanced renal cell carcinoma. This is the first oral multikinase inhibitor that targets serine/threonine and receptor tyrosine kinases in the tumor cell and tumor vasculature. In two preclinical models, it targeted members of two classes of kinases involved in tumor cell proliferation and tumor angiogenesis—two important activities in cancer growth. This ability to block tumor growth may have led to prolonged progression-free survival. Sorafenib also delays the progression of cancer in most patients. Its manageable side-effect profile is a welcome advantage for patients and their oncologists.

Category: Disease

Tags: Oncology, Sorafenib Tosylate, Sunitinib Malate

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