Richard M A, Grob J J, Zarrour H, Bassères N, Bizzari J P, Gérard B, Bonerandi J J
Department of Dermatology, Saint Marguerite's Hospital, Marseille, France.
Melanoma Res. 1998 Apr;8(2):170-4. doi: 10.1097/00008390-199804000-00012.
The combination of dacarbazine (DTIC), cisplatin (DDP), carmustine and tamoxifen (TAM) has been reported to yield a high rate of response in patients with metastatic melanoma, but responders often experience intracranial recurrences. As fotemustine (FOT) has demonstrated activity on cerebral metastases, the rationale of this study was to replace carmustine by FOT in this four-drug regimen. Twenty patients with metastatic melanoma received FOT (100 mg/m2) on days 1 and 8, DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) from day 1 to day 3 and from day 28 to day 30, and continuous daily treatment with TAM (20 mg/day). If stabilization or response was observed at the end of the 8th week, patients received maintenance courses of FOT on day 1, and DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) on days 1 to 3. Nineteen patients were evaluable. Of these, six had brain metastases. The overall response rate was 10.5% (two out of 19); both of the responders had only partial responses. The best responding site was lung. No response was obtained in the four patients with evaluable brain metastases, but no patient had therapy failure due to new brain metastases. The median overall survival was 5 months (range 1-45 months). Toxicity was mainly haematological. The use of this combination is not recommended.
据报道，达卡巴嗪（DTIC）、顺铂（DDP）、卡莫司汀和他莫昔芬（TAM）联合使用对转移性黑色素瘤患者有较高的缓解率，但缓解者常出现颅内复发。由于福莫司汀（FOT）已证明对脑转移瘤有活性，本研究的基本原理是在这个四联方案中用FOT替代卡莫司汀。20例转移性黑色素瘤患者在第1天和第8天接受FOT（100mg/m²），从第1天至第3天以及从第28天至第30天接受DTIC（每天220mg/m²）和DDP（每天25mg/m²），并持续每日服用TAM（20mg/天）。如果在第8周结束时观察到病情稳定或缓解，患者在第1天接受FOT维持疗程，在第1天至第3天接受DTIC（每天220mg/m²）和DDP（每天25mg/m²）。19例患者可评估。其中，6例有脑转移。总缓解率为10.5%（19例中的2例）；两名缓解者均仅为部分缓解。最佳缓解部位是肺部。4例可评估脑转移的患者未获得缓解，但没有患者因新的脑转移而出现治疗失败。中位总生存期为5个月（范围1 - 45个月）。毒性主要是血液学方面的。不推荐使用这种联合方案。
