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Randomized Phase II Study of Gemcitabine and Docetaxel Compared With Gemcitabine Alone in Patients With Metastatic Soft Tissue Sarcomas: Results of Sarcoma Alliance for Research Through Collaboration Study 002

Robert G. Maki, J. Kyle Wathen, Shreyaskumar R. Patel, Dennis A. Priebat, Scott H. Okuno, Brian Samuels, Michael Fanucchi, David C. Harmon, Scott M. Schuetze, Denise Reinke, Peter F. Thall, Robert S. Benjamin, Laurence H. Baker, Martee L. Hensley

From the Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY; Department of Biostatistics & Applied Mathematics and Sarcoma Center, Department of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Washington Cancer Institute, Section of Hematology/Oncology, Washington, DC; Mayo Clinic, Rochester, MN; University of Illinois at Chicago, Oncology Specialists, Park Ridge, IL; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Partners' Health Care/Massachusetts General Hospital Cancer Center, Boston, MA; and the University of Michigan Comprehensive Cancer Center, Ann Arbor, MI

Address reprint requests to Robert G. Maki, MD, PhD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 223, New York, NY 10021; makir{at}mskcc.org

Purpose: Gemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel.

Patients and Methods: In this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions.

Results: One hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999.

Conclusion: Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.

Supported by the Kristen Ann Carr Fund, Eli Lilly & Co, and Sanofi-aventis; and in part by a National Cancer Institute program project Grant No. P01-CA47179, the Shuman Fund for GIST Research, and spin4survival.org (R.G.M.).

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

R.G.M. and J.K.W. contributed equally to this manuscript.

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

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