dacarbazine + fotemustine

A combination chemotherapy regimen consisting of dacarbazine and fotemustine used primarily for the treatment of metastatic malignant melanoma. This combination has been studied in various clinical trials with different dosing schedules and sometimes in combination with other agents. ## Treatment Protocol The typical administration protocol involves: - **Induction treatment**: - Fotemustine 100 mg/m² on days 1 and 8 - Dacarbazine 250 mg/m² daily on days 15-18 - Followed by a 4-5 week rest period[1] - **Maintenance treatment** (for responding or stabilized patients): - Fotemustine 100 mg/m² on day 1 - Dacarbazine 250 mg/m² on days 2-5 - Repeated every 3 weeks[1] ## Clinical Efficacy In a multicentric study involving 63 evaluable patients with disseminated malignant melanoma, this combination demonstrated: - Overall response rate of 33.3% (9 complete responses and 12 partial responses) - Effectiveness in pretreated patients (34.9% response rate) - Activity against cerebral metastases (28.6% response rate) - Response in visceral metastases (23.1%) - Particularly good activity against non-visceral metastases (43.3%)[1] ## Toxicity Profile The main toxicity observed was hematological: - Grade III/IV leukopenia: 22.2% of patients - Grade III/IV thrombocytopenia: 20.3% of patients[1] Overall, the toxicity was considered acceptable in the context of the treatment's efficacy. ## Alternative Administration Schedules Research has explored different administration schedules, including sequential administration where fotemustine is given 4 hours after dacarbazine, based on the theory that dacarbazine might deplete O6-alkylguanine-DNA-alkyltransferase (ATase), potentially enhancing fotemustine's effectiveness[4]. Another study investigated a four-drug regimen replacing carmustine with fotemustine in combination with dacarbazine, cisplatin, and tamoxifen, but this particular combination showed limited efficacy with only a 10.5% response rate[2]. The timing of administration appears important, as one study noted that administering fotemustine 1 hour prior to dacarbazine showed unexpected antagonism and modified toxicity patterns[4].