Fotemustine and carboplatine vs fotemustine alone in patients with metastatic melanoma: prospective non-randomized pilot trial

Background. Metastatic melanoma in most cases remains incurable disease. Current treatment options are limited and mainly consist of systemic treatment such as dacarbazine with or without other chemotherapeutic agents. We have investigated new chemotherapy regimen, which combines two potent drugs fotemustine and carboplatin and compared it to fotemustine alone. Patients and methods. Between March and August 2008 37 patients with metastatic melanoma were included. 18 pts received fotemustine + carboplatin (group 1) and 19 pts received fotemustine alone (group 2). Both groups did not differ significantly in baseline characteristics (age, sex, stage and number of involved sites). Three pts in group 1 and 10 in group 2 had been never treated for metastatic melanoma. Fourteen and 13 pts had cutaneous melanoma in group 1 and 2 respectively; other patients had uveal melanoma, mucosal melanoma and metastases from UPO. The schedule of fotemustine infusions was the same in both arms: induction consists of fotemustine 100 mg/m² on day 1, 8 and 15 followed by the 5 week treatment-free interval. If no progression was detected, supportive cycles of fotemustine 100 mg/m² on day 1 were performed every 28 days. In combination group carboplatin (AUC=5) administered each cycle on day 2. Results. According to RECIST we registered 2 complete responses and 1 partial response, 6 pts were stable in group 1; in group 2 only 1 partial response was detected, 8 pts remained stable (р>0,5). Median PFS was 3,7 (95% CI 1 to 6.4) months and 3,1 (95% CI 0,8 to 5,4) months in group 1 and 2 respectively (р>0,53). Median OS in group 2 was 11,9 months, and median OS in group 1 is still not reached. Both treatments were comparable in respect to toxicity they induced. Most common side effects were trombocytopenia (grade 3-4 7/18 and 6/19 pts for group 1 and 2 respectively) and neutropenia (grade 3-4 7/18 and 5/19 pts for group 1 and 2 respectively). In one patient from group 1 non-fatal brain hemorrhage occurred. Conclusion. No significant benefit from combined treatment with fotemustine and carboplatin were revealed, so we do not recommend this regimen for routine use in advanced melanoma. Higher frequency of objective responses in combined treatment group should be proven in well-organized controlled trials.

metastatic melanoma, fotemustine, carboplatin