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Dacarbazine, Cisplatin, and Interferon-Alfa-2b With or Without Interleukin-2 in Metastatic Melanoma: A Randomized Phase III Trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group

From the Department of Medicine III, Charité, Campus Benjamin Franklin, Berlin; Department of Dermatology, University of Ulm, Ulm; Department of Dermatology, University of Heidelberg, Heidelberg; Haematologisch-Onkologische Praxis Altona, Hamburg, Germany; Department of Medical Oncology, University Medical Center, Nijmegen; Daniel den Hoed Cancer Center, University of Rotterdam, Rotterdam, Netherlands; Royal Marsden Hospital, London; Cancer Research UK Clinical Center, St James’s University Hospital, Leeds, United Kingdom; Centre Pluridisciplinaire d’Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Oncology, University Hospital Gasthuisberg, Leuven; European Organisation for Research and Treatment of Cancer Data Center; Department d’Oncologie, Hospital Universitaire Erasme, Brussels, Belgium; and Department of Medical Oncology, Centre Leon Berard, Lyon, France

Address reprint requests to Ulrich Keilholz, MD, Department of Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany; e-mail: ulrich.keilholz{at}medizin.fu-berlin.de

BACKGROUND: Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma.

PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m² and cisplatin 30 mg/m² on days 1 to 3 combined with interferon-alfa-2b 10 x 10⁶ U/m² subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 x 10⁶ U/m²/6 hours, 18 x 10⁶ U/m²/12 hours, 18 x 10⁶ U/m²/24 hours, and 4.5 x 10⁶ U/m² for 3 x 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles.

RESULTS: Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%).

CONCLUSION: Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.

Supported by educational grants from Chiron BV (Amsterdam, Netherlands), Schering Plough (Kenilworth, NJ), and the National Cancer Institute (Bethesda, MD; grants 2U10 CA11488-25 through 5U10 CA11488-32).

The article’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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

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