Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies

Department of Oncology (R4), Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
British Journal of Cancer (Impact Factor: 4.82). 07/2011; 105(3):353-9. DOI: 10.1038/bjc.2011.257
Source: PubMed

ABSTRACT The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study.
In the phase I study, three patients were treated with sorafenib 200 mg twice daily (b.i.d.) plus 1000 mg m(-2) dacarbazine on day 1 of a 21-day cycle and 15 patients had the sorafenib dose escalated to 400 mg b.i.d. without reaching the maximum tolerated dose of the combination. In the phase II study (n=83), the overall response rate was 12% (95% CI: 6, 21): one complete and nine partial, with median response duration of 46.7 weeks. Stable disease was the best response in 37%; median duration was 13.3 weeks. Median overall survival (OS) was 37.0 weeks (95% CI: 33.9, 46.0).
Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.

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