INTERFERON-ALPHA-2B AND FOTEMUSTINE IN PATIENTS WITH DISSEMINATED MELANOMA - A MULTICENTER PHASE-II TRIAL OF THE AIO PHASE-I PHASE-II STUDY-GROUP OF THE GERMAN-CANCER-SOCIETY

Background: The introduction of r-Interferon alpha (rIfn alpha) into c ytostatic chemotherapy of metastatic melanoma appears to improve objec tive remission rates. Favorable results of early clinical and single i nstitution trials, however, generally could not be confirmed by prospe ctive multicenter studies. With the introduction of fotemustine (FM), a chloro-nitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU-radical, a new active compound became available for the treatment of patients with melanoma, yielding an ob jective remission rate of 12% (95% CI 6-20%; EORTC 1995). Methods: Hop ing for an improvement of this modest response rate, a controlled mult icenter phase I/II study was started, combining rIfn alpha 2b (10 MU s .c. day 1-28) with FM, initially for 2-, thereafter for 3-weekly doses of 100 mg/m(2) at days 14, 21, and 28, followed by a 5-week rest peri od. Results: Out of 31 patients 28 were eligible and evaluable for saf ety, 26 evaluable for efficacy. We observed 1 complete and 1 partial r emission (7.7%, 95% CI 0.9-25.1%), no change occurred in 6 out of 26 ( 23%). In 24 patients treatment was terminated because of tumor progres sion. Toxicity was well within acceptable limits and similar to FM alo ne: Up to 10% WHO grade III thrombocytopenia, 20% grade III and IV gra nulocytopenia, and moderate gastrointestinal tract toxicity with 10% g rade III and 3% grade IV nausea and vomiting, despite conventional ant iemetic medication. Conclusions: rIfn alpha 2b in the schedule and dos e tested does not seem to improve remission rates of FM alone and may be disadvantageous both in terms of tumor response and quality of life .