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

T Eisen, R Marais, A Affolter, P Lorigan, C Robert, P Corrie, C Ottensmeier, C Chevreau, D Chao, P D Nathan, T Jouary, M Harries, S Negrier, E Montegriffo, T Ahmad, I Gibbens, M G James, U P Strauss, S Prendergast, M E Gore, T Eisen, R Marais, A Affolter, P Lorigan, C Robert, P Corrie, C Ottensmeier, C Chevreau, D Chao, P D Nathan, T Jouary, M Harries, S Negrier, E Montegriffo, T Ahmad, I Gibbens, M G James, U P Strauss, S Prendergast, M E Gore

Abstract

Method: 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.

Results: 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).

Conclusion: Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.

Conflict of interest statement

E Montegriffo, UP Strauss, and S Prendergast are employees of Bayer Pharmaceuticals. T Eisen receives research support from Bayer and has received honoraria for advisory boards and speaking engagements. R Marais has received honoraria and research support from Bayer Healthcare Pharmaceuticals. PD Nathan has received honoraria for advisory boards and speaking engagements for Bayer Healthcare. T Jouary has received honoraria for consulting from Bristol Myer Squibb. I Coombes received financial support from Bayer Healthcare to attend meetings (2004). ME Gore is funded by the National Institute for Health Research, UK. A Affolter, P Lorigan, C Robert, P Corrie, C Ottensmeier, M Harries, MG James, C Chevreau, D Chao, S Negrier, and T Ahmad declare no conflict of interest.

Figures

Figure 1
Figure 1
Phase II study: percentage change in tumour burden with time.
Figure 2
Figure 2
Phase II study Kaplan–Meier plots: (A) overall survival and (B) time to progression. Data available from 78 subjects for time to progression.

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