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Sorafenib tosylate is a drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer (hepatocellular carcinoma). On November 16, 2007, the FDA approved sorafenib tosylate (CAS NO:475207-59-1), a small molecule Raf kinase and VEGF receptor kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC), a type of liver cancer. In November 2009, the UK's National Institute of Clinical Excellence declined to approve the drug for use within the NHS in England, Wales and Northern Ireland, stating that its effectiveness (increasing survival in primary liver cancer by 6 months) did not justify its high price, at up to £3000 per patient per month. In Scotland the drug had already been refused authorization by the Scottish Medicines Consortium for use within NHS Scotland, for the same reason. In March 2012, the Indian Patent Office granted a domestic company, Natco Pharma, a license to manufacture generic Sorafenib, bringing its price down by 97%. Bayer sells a month's supply, 120 tablets, of Nexavar for INR280000 (US$4,300). Natco Pharma will sell 120 tablets for INR8800 (US$130), while still paying a 6% royalty to Bayer. Under Indian Patents Act, 2005 and the World Trade Organisation TRIPS Agreement, the government can issue a compulsory license when a drug is not available at an affordable price. The current approval was based on the results of an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with unresectable, biopsy-proven hepatocellular carcinoma. Overall survival was the primary efficacy endpoint. A total of 602 patients were randomized; 299 to sorafenib 400 mg twice daily and 303 to matching placebo. Demographics and baseline disease characteristics were similar between the sorafenib and placebo groups. Prior treatments included surgical resections (20 percent), locoregional therapies (including radiofrequency ablation, percutaneous ethanol injection and transarterial chemoembolization in 40 percent), radiotherapy (5 percent), and systemic therapy (4 percent). The trial was stopped following a pre-specified second interim analysis for survival disclosing a statistically significant advantage for sorafenib [median 10.7 vs. 7.9 months; HR: 0.69 (95 percent CI: 0.55, 0.87), p= 0.00058]. The final analysis of time-to-tumor progression (TTP) by independent radiologic review was based on data from an earlier time point and demonstrated a statistically significant improvement in TTP in the sorafenib arm [median 5.5 vs. 2.8 months; HR: 0.58 (95 percent CI: 0.45, 0.74), p=0.000007]. The most common adverse reactions (=20 percent) considered related to Sorafenib tosylate were fatigue, weight loss, rash/ desquamation, hand-foot skin reaction, alopecia, diarrhea, anorexia, nausea and abdominal pain. Diarrhea was reported in 55 percent of Sorafenib tosylate patients (grade 3 in 10 percent). Hand-foot syndrome (21 percent overall; grade 3 in 8 percent) and rash (19 percent overall; grade 3 in 1 percent) were the most common dermatologic adverse reactions toSorafenib tosylate. Cardiac ischemia or infarction was reported in 2.7 percent of Sorafenib tosylate patients (1.3 percent placebo). Treatment-emergent hypertension was reported in 9 percent of Sorafenib tosylate patients (4 percent placebo). Grade 3 hypertension was reported in 4 percent of Sorafenib tosylate patients (1 percent placebo). Elevated serum lipase occurred in 40 percent of Sorafenib tosylate patients (37 percent placebo), and hypophosphatemia occurred in 35 percent of Sorafenib tosylate patients (11 percent placebo). Want to learn more information about Sorafenib tosylate, you can access the guidechem.com. Guidechem.com is just a place for you to look for some chemicals.
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