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lüll Sorafenib for the treatment of unresectable hepatocellular carcinoma Kane RC; Farrell AT; Madabushi R; Booth B; Chattopadhyay S; Sridhara R; Justice R; Pazdur ROncologist 2009[Jan]; 14 (1): 95-100PURPOSE: To describe the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar; Bayer Pharmaceuticals Corp., Montville, NJ, and Onyx Pharmaceuticals Corp., Emeryville, CA), an oral kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The FDA independently analyzed an international, double-blind, placebo-controlled trial comparing the effect of best supportive care plus sorafenib or matching placebo on overall survival. Eligible patients had unresectable, biopsy-proven HCC and had not received prior systemic therapy. RESULTS: Among the 602 randomized patients (placebo, 303; sorafenib, 299), baseline characteristics were well balanced, and 97% were Child-Pugh score A. HCC was "advanced" in 70% overall, as defined by extrahepatic metastases or by tumor radiographically visible in venous structures outside the liver. Underlying liver diseases included hepatitis B (18%), hepatitis C (28%), and alcohol-related (26%). The trial was stopped following a prespecified second interim analysis showing a statistically significant survival advantage for sorafenib [median, 10.7 vs 7.9 months; hazard ratio, 0.69 (95% confidence interval, (0.55, 0.87)), p = 0.00058]. Adverse events in sorafenib-treated patients included diarrhea in 55% (grade 3, 10%), hand-foot syndrome in 21% (grade 3, 8%), rash in 19% (grade 3, 1%), and cardiac ischemia or infarction in 2.7% (versus 1.3% for placebo). On sorafenib, treatment-emergent hypertension occurred in 9% of patients (placebo, 4%) and was grade 3 in 4% (placebo, 1%); elevated serum lipase occurred in 40% (placebo, 37%); hypophosphatemia occurred in 35% (placebo, 11%). CONCLUSIONS: Sorafenib is the first systemic therapy to demonstrate a survival benefit in a randomized trial for unresectable HCC and has received FDA approval for this indication.|Antineoplastic Agents/adverse effects/*therapeutic use[MESH]|Benzenesulfonates/adverse effects/*therapeutic use[MESH]|Carcinoma, Hepatocellular/*drug therapy[MESH]|Drug Approval[MESH]|Humans[MESH]|Liver Neoplasms/*drug therapy[MESH]|Niacinamide/analogs & derivatives[MESH]|Phenylurea Compounds[MESH]|Protein Kinase Inhibitors/adverse effects/*therapeutic use[MESH]|Pyridines/adverse effects/*therapeutic use[MESH]|Randomized Controlled Trials as Topic[MESH]|Sorafenib[MESH]|United States[MESH]|United States Food and Drug Administration[MESH] |