Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma

Inspired by the high response rates achieved with the DBCT regimen (dacarba zine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administ ered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m(2)) and cisp latin (100 mg/m(2)) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sam pling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response r ate of 22.7% (95% confidence interval 12.9-32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocyt openia, protracted nausea/vomiting end ototoxicity. Renal toxicity was gene rally mild, but possibly contributed to two deaths, Seven patients experien ced deep venous thrombosis during the study. TAM had no influence on the ph armacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment, However, a recent publication concludes that the latter achieves a considerably lower respons e rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered rou tinely to unselected patients. Considering the number of potentially seriou s side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients. (C) 1998 Lippincott Will iams & Wilkins.