Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and treatment effectiveness. A multicentre phase II trial of the EORTC-Melanoma Cooperative Group (MCG).

Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2 on days 1 + 8 + 15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligible vs non-eligible patient group (in parentheses) were as follows: male/female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0-1 (0-4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4-16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III+IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes