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: 4.84). 07/2011; 105(3):353-9. DOI: 10.1038/bjc.2011.257
Source: PubMed


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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    • "The sorafenib dose (400 mg b.i.d) is administered in combination with standard chemotherapy, such as dacarbazine, in patients with advanced melanoma because it has few side effects as a single agent, indeed the response rate was 21% with a median time from treatment initiation of 2.3 months (26). Although this combination does not cause toxic effects and shows antitumor activity, it is not applied in clinical practice because selective inhibitors of B-RAF are more effective in the treatment of malignant melanoma (27). "
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