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High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993

From the Cytokine Working Group and Surgery Branch, National Cancer Institute, Bethesda, MD; Modified Group C Program; and Chiron Corp, Emeryville, CA.

Address reprint requests to Michael B. Atkins, MD, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, E/KS-158, Boston, MA 02215.

PURPOSE: To determine the short- and long-term efficacy and toxicity of the high-dose intravenous bolus interleukin 2 (IL-2) regimen in patients with metastatic melanoma.

PATIENTS AND METHODS: Two hundred seventy assessable patients were entered onto eight clinical trials conducted between 1985 and 1993. IL-2 (Proleukin [aldesleukin]; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Data were analyzed through fall 1996.

RESULTS: The overall objective response rate was 16% (95% confidence interval, 12% to 21%); there were 17 complete responses (CRs) (6%) and 26 partial responses (PRs) (10%). Responses occurred with all sites of disease and in patients with large tumor burdens. The median response duration for patients who achieved a CR has not been reached and was 5.9 months for those who achieved a PR. Twelve (28%) of the responding patients, including 10 (59%) of the patients who achieved a CR, remain progression-free. Disease did not progress in any patient responding for more than 30 months. Baseline performance status and whether patients had received prior systemic therapy were the only predictive prognostic factors for response to IL-2 therapy. Toxicities, although severe, generally reversed rapidly after therapy was completed. Six patients (2%) died from adverse events, all related to sepsis.

CONCLUSION: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.

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				S. J. O'Day, P. D. Boasberg, L. Piro, T. S. Kristedja, H.-J. Wang, M. Martin, R. Deck, P. Ames, K. Shinn, H. Kim, et al. Maintenance Biotherapy for Metastatic Melanoma with Interleukin-2 and Granulocyte Macrophage-Colony Stimulating Factor Improves Survival for Patients Responding to Induction Concurrent Biochemotherapy Clin. Cancer Res., September 1, 2002; 8(9): 2775 - 2781. [Abstract] [Full Text] [PDF]

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				I. Espinoza-Delgado Cancer Vaccines Oncologist, August 1, 2002; 7(90003): 20 - 33. [Abstract] [Full Text] [PDF]

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				R. Ridolfi, V. Chiarion-Sileni, M. Guida, A. Romanini, R. Labianca, A. Freschi, G. Lo Re, R. Nortilli, S. Brugnara, P. Vitali, et al. Cisplatin, Dacarbazine With or Without Subcutaneous Interleukin-2, and Interferon Alfa-2b in Advanced Melanoma Outpatients: Results From an Italian Multicenter Phase III Randomized Clinical Trial J. Clin. Oncol., March 15, 2002; 20(6): 1600 - 1607. [Abstract] [Full Text] [PDF]

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				S. S. Agarwala, J. Glaspy, S. J. O'Day, M. Mitchell, J. Gutheil, E. Whitman, R. Gonzalez, E. Hersh, L. Feun, R. Belt, et al. Results From a Randomized Phase III Study Comparing Combined Treatment With Histamine Dihydrochloride Plus Interleukin-2 Versus Interleukin-2 Alone in Patients With Metastatic Melanoma J. Clin. Oncol., January 1, 2002; 20(1): 125 - 133. [Abstract] [Full Text] [PDF]

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