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Fotemustine Compared With Dacarbazine in Patients With Disseminated Malignant Melanoma: A Phase III Study

From the Institut Gustave Roussy, Villejuif; CHU Sainte-Marguerite; CHRU de la Timone, Marseille; Centre Oscar Lambret, Lille; CHU Ambroise Paré, Boulogne Billancourt; Hôpital Beaujon, Clichy; Hôpital Foch, Suresnes, France; Universitäts-Hautklinik, Kiel; Dermatologisches Zentrum, Buxtehude; Allg. Krankenhaus St. Georg; Universitäts Krankenhaus Eppendorf, Hamburg; Friedrichs-Wihelms-Universitäts, Bonn; Fachklinik Hornheide, Münster, Germany; National Institute of Oncology, Budapest, Hungary; Norwegian Radium Hospital, Oslo, Norway; Instituto Valenciano de Oncología, Valencia; Clinica CONIM, Madrid; Hospital Central de Asturias, Oviedo, Spain; Allg. Krankenhaus, Wien, Austria; and Prednosta Internej Kliniky, Brastislava, Slovakia

Address reprint requests to Marie Françoise Avril, MD, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejiuf Cedex, France; e-mail: avril{at}igr.fr

PURPOSE: To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma.

PATIENTS AND METHODS: Patients received either intravenous fotemustine 100 mg/m² weekly for 3 weeks or DTIC 250 mg/m²/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m² or DTIC 250 mg/m² for 5 days).

RESULTS: Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n = 229; 15.2% v 6.8%; P = .043) and in full analysis set (n = 221) (15.5% v 7.2%; P = .053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P = .059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P = .067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms.

CONCLUSION: ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

This work was supported by the Institut de Recherches Internationales Servier, Courbevoie, France.

This work was presented at the Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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