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Phase I/II Trial of Temsirolimus Combined With Interferon Alfa for Advanced Renal Cell Carcinoma

Robert J. Motzer, Gary R. Hudes, Brendan D. Curti, David F. McDermott, Bernard J. Escudier, Sylvie Negrier, Brigitte Duclos, Laurence Moore, Timothy O'Toole, Joseph P. Boni, Janice P. Dutcher

From the Memorial Sloan-Kettering Cancer Center, New York; Our Lady of Mercy Cancer Center/New York Medical College, Bronx, NY; Fox Chase Cancer Center, Philadelphia; Wyeth Research, Collegeville, PA; Robert W. Franz Cancer Research Center, Portland, OR; Beth Israel Deaconess Medical Center, Boston, MA; Institut Gustave-Roussy, Villejuif; Centre Leon Berard, Lyon; University Hospital of Strasbourg-Hautepierre, Strasbourg, France; and Wyeth Research, Cambridge, MA

Address reprint requests to Robert J. Motzer, MD, Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: motzerr{at}mskcc.org

Purpose Temsirolimus, an inhibitor of the mammalian target of rapamycin, has single-agent activity against advanced renal cell carcinoma (RCC). A recommended dose and safety profile for the combination of temsirolimus and interferon alfa (IFN) were determined in patients with advanced RCC.

Patients and Methods Patients were enrolled onto a multicenter, ascending-dose study of temsirolimus (5, 10, 15, 20, or 25 mg) administered intravenously once a week combined with IFN (6 or 9 million units [MU]) administered subcutaneously three times per week. An expanded cohort was treated at the recommended dose to obtain additional safety and efficacy information.

Results Seventy-one patients were entered to receive one of six dose levels. The recommended dose was temsirolimus 15 mg/IFN 6 MU based on dose-limiting toxicities of stomatitis, fatigue, and nausea/vomiting, which were observed at higher doses of temsirolimus and IFN. The most frequent grade 3 or 4 toxicities occurring in any cycle included leukopenia, hypophosphatemia, asthenia, anemia, and hypertriglyceridemia for all patients and those who received the recommended dose. Among patients who received the recommended dose (n = 39), 8% achieved partial response and 36% had stable disease for at least 24 weeks. Median progression-free survival for all patients in the study was 9.1 months.

Conclusion The combination of temsirolimus and IFN has an acceptable safety profile and displays antitumor activity in patients with advanced RCC. Temsirolimus 15 mg plus IFN 6 MU is the recommended dose for evaluation in a randomized phase III study.

Supported by Wyeth Research, Cambridge, MA.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 1, 2003, Chicago, IL, and at the 40th Annual Meeting of the American Society of Clinical Oncology, June 7, 2004, New Orleans, LA.

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

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