Originally published as JCO Early Release 10.1200/JCO.2003.02.014 on June 16 2003

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Adjuvant High-Dose Bolus Interleukin-2 for Patients With High-Risk Renal Cell Carcinoma: A Cytokine Working Group Randomized Trial

Joseph I. Clark, Michael B. Atkins, Walter J. Urba, Steven Creech, Robert A. Figlin, Janice P. Dutcher, Larry Flaherty, Jeffrey A. Sosman, Theodore F. Logan, Richard White, Geoffrey R. Weiss, Bruce G. Redman, Christopher P.G. Tretter, David McDermott, John W. Smith, Michael S. Gordon, Kim A. Margolin

From the Loyola University Chicago, Maywood, IL; Beth Israel Deaconess Medical Center, Boston, MA; Earle A. Chiles Research Institute/Providence Portland Medical Center, Portland, OR; University of California at Los Angeles, Los Angeles; City of Hope National Medical Center, Duarte, CA; Our Lady of Mercy Comprehensive Cancer Center, New York, NY; Wayne State University, Detroit; University of Michigan, Ann Arbor, MI; Vanderbilt University, Nashville, TN; Indiana University, Indianapolis, IN; Carolinas Medical Center, Charlotte, NC; University of Texas/South Texas Veterans Health Care System, San Antonio, TX; Dartmouth Hitchcock Medical Center, Lebanon, NH; and Arizona Health Sciences Center, Phoenix, AZ.

Address reprint requests to Joseph I. Clark, MD, Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153; email: jclark{at}lumc.edu.

Purpose: This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC).

Patients and Methods: Eligibility requirements were resected locally advanced (LA; T3b-4 or N1–3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history.

Results: Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P = .73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P = .38). Analysis including metastasectomy patients made no difference in DFS or overall survival.

Conclusion: One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.

Supported by an unrestricted educational grant from Chiron Corp, Emeryville, CA.

Presented at the 39th Annual Meeting of the American Society of Clinical Oncology, June 1, 2003, Chicago, IL.

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