Originally published as JCO Early Release 10.1200/JCO.2005.01.1551 on October 31 2005

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Temozolomide in Combination With Interferon-Alfa Versus Temozolomide Alone in Patients With Advanced Metastatic Melanoma: A Randomized, Phase III, Multicenter Study from the Dermatologic Cooperative Oncology Group

Roland Kaufmann, Konstanze Spieth, Ulrike Leiter, Cornelia Mauch, Peter von den Driesch, Thomas Vogt, Ruthild Linse, Wolfgang Tilgen, Dirk Schadendorf, Jürgen C. Becker, Günther Sebastian, Sven Krengel, Lutz Kretschmer, Claus Garbe, Reinhard Dummer

From the Departments of Dermatology, J.W. Goethe-University, Frankfurt am Main; University of Tübingen, Tübingen; University of Köln, Cologne; University of Erlangen, Erlangen/Stuttgart; University of Regensburg, Regensburg; Helios Clinic Erfurt, Erfurt; Saarland University, Homburg; Skin Cancer Unit, German Cancer Research Center, Mannheim; University of Würzburg, Würzburg; University of Dresden, Dresden; University of Schleswig-Holstein Campus Lübeck, Lübeck; University of Göttingen, Göttingen, Germany; and University of Zürich, Switzerland

Please address reprint requests to Konstanze Spieth, MD, Department of Dermatology, J.W. Goethe-University, Frankfurt am Main, Germany; e-mail: konstanze.spieth{at}kgu.de.

PURPOSE: Temozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN- in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial.

PATIENTS AND METHODS: Two hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m²/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN- (5 MU/m²; days 1, 3, and 5 every week).

RESULTS: Two hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN- arm, 33 (24.1%) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN- arm (P < .001).

CONCLUSION: In metastatic melanoma treatment with TMZ + IFN- leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.

Supported by grants from Essex Pharma GmbH (Munich, Germany).

R.K. and K.S. are co-senior authors.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

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

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