Originally published as JCO Early Release 10.1200/JCO.2008.17.5448 on November 10 2008

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Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group

Michael B. Atkins, Jessie Hsu, Sandra Lee, Gary I. Cohen, Lawrence E. Flaherty, Jeffrey A. Sosman, Vernon K. Sondak, John M. Kirkwood

From the Beth Israel Deaconess Medical Center; Dana-Farber Cancer Institute, Boston, MA; Greater Baltimore Medical Center, Baltimore, MD; Wayne State University, Detroit, MI; Vanderbilt University, Nashville, TN; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and the University of Pittsburgh Medical Center, Pittsburgh, PA

Corresponding author: Michael B. Atkins, MD, Beth Israel Deaconess Medical Center, MASCO Rm 412, 375 Longwood Ave, Boston, MA 02215; e-mail: matkins{at}bidmc.harvard.edu

Purpose Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup.

Patients and Methods Patients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months.

Results Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001).

Conclusion Although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.

published online ahead of print at www.jco.org on November 10, 2008.

Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA16116, CA80775, CA39229, CA14028, CA74811, CA32102, CA27057, and CA38926 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair).

The contents of this article 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 and author contributions are found at the end of this article.

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