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

被引：32

作者：

Eisen, T. ^{[1
]}

Marais, R. ^{[2
]}

Affolter, A. ^{[2
]}

Lorigan, P. ^{[3
]}

Robert, C. ^{[4
]}

Corrie, P. ^{[1
]}

Ottensmeier, C. ^{[5
]}

Chevreau, C. ^{[6
]}

Chao, D. ^{[7
]}

Nathan, P. D. ^{[8
]}

Jouary, T. ^{[9
]}

Harries, M. ^{[10
]}

Negrier, S. ^{[11
]}

Montegriffo, E. ^{[12
]}

Ahmad, T. ^{[13
]}

Gibbens, I. ^{[13
]}

James, M. G. ^{[13
]}

Strauss, U. P. ^{[14
]}

Prendergast, S. ^{[12
]}

Gore, M. E. ^{[13
]}

机构：

[1] Addenbrookes Hosp, Dept Oncol R4, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

[2] Inst Canc Res, Div Canc Biol, London SW3 6JB, England

[3] Christie Hosp, Dept Med Oncol, Manchester M20 4BX, Lancs, England

[4] Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France

[5] Southampton Univ Hosp, Canc Sci Div, Southampton SO16 6YD, Hants, England

[6] Inst Claudius Regaud, Dept Med Oncol, F-31052 Toulouse, France

[7] Royal Free Hosp, Canc Serv Div, London NW3 2QG, England

[8] Mt Vernon Canc Ctr, Canc Serv Div, Northwood HA6 2RN, Middx, England

[9] Hop St Andre, Dept Dermatol, F-33075 Bordeaux, France

[10] Guys & St Thomas Hosp, Canc Serv Div, London SE1 7EH, England

[11] Ctr Leon Berard, F-39373 Lyon, France

[12] Bayer PLC, Newbury RG14 1JA, Berks, England

[13] Royal Marsden Hosp, Dept Med, London SW3 6JJ, England

[14] Bayer Schering Pharma, D-51368 Leverkusen, Germany

来源：

BRITISH JOURNAL OF CANCER | 2011年 / 105卷 / 03期

关键词：

melanoma; sorafenib; dacarbazine; combination therapy; biomarker; RANDOMIZED DISCONTINUATION TRIAL; AMERICAN-JOINT-COMMITTEE; MULTIKINASE INHIBITOR; MALIGNANT-MELANOMA; COMBINATION; RAF; BRAF; TEMOZOLOMIDE; CARBOPLATIN; MUTATIONS;

D O I：

10.1038/bjc.2011.257

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. British Journal of Cancer (2011) 105, 353-359. doi:10.1038/bjc.2011.257 www.bjcancer.com Published online 12 July 2011 (C) 2011 Cancer Research UK

引用

页码：353 / 359

页数：7

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