Nexavar for pancreatic cancer
Nexavar(sorefenib) is currently FDA approved for renal cell carcinoma and hepatocellular carcinoma . Sorafenib (Nexavar) is designed to interfere with growth of new blood vessels and the growth of new cancer cells byinhibiting various cell growth adn differentiation pathways.
This mechanism of action provoked an interest is using this drug for other solid cancers, especially for pancreatic cancer, where new agents are sorely needed. A single-centre, open-label, phase I dose-escalation study was performed to investigate sorafenib combined with irinotecan, a chemo drug, in patients with advanced, refractory solid tumours. Thirty-four patients were treated: 20 in the dose-escalation phase (common tumour types: CRC [45%], ovarian [5%], pancreatic [5%]) and 14 patients in the extension phase of the study. Stable disease was achieved in 12/20 (60%) evaluable patients in cohorts 1–3, and 10/13 (77%) evaluable patients in cohort 4. A further patient from cohort 4 had a partial response of >200 days. The investigators concluded: “Sorafenib 400 mg bid can be combined with irinotecan 125 mg/m2 or 140 mg for the treatment of patients with advanced, refractory solid tumours, although monitoring for toxicity is recommended.”
Although a phase I study by Siu was promising, a phase II study of gemcitabine/sorafenib combination showed that these combination was inactive for pancreatic cancer(Wallace et al). Data from the BAYPAN study presented at the American College of Clinical Oncology’s 2011 Annual Meeting did not support the addition of sorafenib to gemcitabine therapy in the treatment of advanced pancreatic cancer (APC). Anthony Goncalves, MD, of the Institut Paoli-Calmettes, Marseilles, France, and colleagues noted that this is in contrast to an earlier Phase I study(Siu et al) that demonstrated that the gemcitabine (G) + sorafenib (S) combination was well tolerated and had activity in APC patients. Unfortunately, similar results were obtained in studies of sorafenib with other combinations of drugs, such as erlotinib , cisplatin and capecitabine.
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