Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma

Abstract

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.

Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor-prognosis non-small-cell lung cancer

“…An OR rate of 12% was observed but the treatment was associated with a 30% grade IV thrombopenia toxicity. It has been observed, in a more recent study of fotemustine 100 mg m-2 in melanoma, that the day 1, day 8 schedule is well tolerated with a similar efficacy (Avril et al, 1990 We report herein a French multicentre phase II study on fotemustine on day 1 and day 8 in patients with poorprognosis advanced NSCLC. …”

“…Among NSCLC patients, those who relapse after first-line chemotherapy or those presenting central nervous system metastases are considered to have poor prognosis and are usually ineligible for cisplatin-based therapy. Thus, a search for new drugs is required in an attempt to obtain a survival advantage without inacceptable toxicity, particularly in patients with poor-prognosis NSCLC.Fotemustine, a new amino acid phosphonate derivative of the nitrosourea group, has been recently introduced in the treatment of human solid malignancies (Avril et al, 1990;Jacquillat et al, 1990a). This cytotoxic drug induced a 24% objective response (OR) rate in a phase II study of fotemustine as a single-drug therapy in disseminated malignant melanoma (Jacquillat et al, 1990a), including patients with brain metastases (Jacquillat et al, 1990b).…”

“…Fotemustine, a new amino acid phosphonate derivative of the nitrosourea group, has been recently introduced in the treatment of human solid malignancies (Avril et al, 1990;Jacquillat et al, 1990a). This cytotoxic drug induced a 24% objective response (OR) rate in a phase II study of fotemustine as a single-drug therapy in disseminated malignant melanoma (Jacquillat et al, 1990a), including patients with brain metastases (Jacquillat et al, 1990b).…”

Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme

“…Furthermore, a synergistic effect among the combination of D and F was observed in melanoma cell lines, in patients with disseminated malignant melanoma and recurrent GBM (Fischel et al, 1990;Aamdal et al, 1992;Avril et al, 1990). F, (diethyl 1-(3-(2 chloroethyl) 3 nitrosoureido) ethyl phosphonate) is an alkylating agent characterised by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilia and a high brain permeability coefficient.…”

TDiscovery and Development of Novel Therapeutic Agents for Advanced Melanoma

“…In most of these trials, only 10~20% response rates were observed. There was little evidence to suggest superiority of these combinations compared with DTIC treatment alone (31)(32)(33).…”