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Initial Clinical Response Predicts Outcome and Is Associated With Dose Schedule in Metastatic Melanoma and Renal Cell Carcinoma Patients Treated With High-Dose Interleukin 2

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Abstract

Background

High-dose interleukin (IL)-2 is an effective agent for the treatment of metastatic malignant melanoma and renal cell carcinoma. This study evaluated the outcomes of patients receiving two commonly used intravenous IL-2 schedules that have never been directly compared.

Methods

Forty-seven metastatic malignant melanoma and renal cell carcinoma patients were identified from a prospective database who underwent high-dose IL-2 therapy (720,000 or 600,000 IU/kg) during 1999 to 2003. Disease-specific survival (DSS) was calculated by the Kaplan-Meier method with the log-rank test on an intention-to-treat basis. Multivariate Cox regression analysis of prognostic variables associated with outcome was performed. Factors associated with initial response and prevention of disease progression were determined.

Results

Objective response (5 partial and 5 mixed) or disease stabilization was noted in 9 (20%) and 10 (22%), respectively, of 46 assessable patients after 1 course of therapy. Four patients (22%) achieved disease-free status after the third course of IL-2 (n = 1) or surgical resection of confined metastatic disease (n = 3). At 19.1 months’ median follow-up, factors associated with improved DSS included an initial clinical response to IL-2 therapy (P < .001) and a higher administered dose (P = .04). Patients who received 720,000 IU/kg were more likely to experience an initial major objective response (P = .03) and disease stabilization (P = 0.03) independent of the tumor treated. Objective response early in the course of therapy was the only independent predictor of tumor-related mortality (P = .004).

Conclusions

The initial clinical response to IL-2 therapy is an independent predictor of improved outcome associated with DSS and the 720,000 IU/kg dose. These results support further prospective trials with increased IL-2 dose schedules in a larger cohort of patients.

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Acknowledgments

Supported by grants from the National Institutes of Health (K08–79881), the National Cancer Institute (R01-093696), and the Doris Duke Charitable Foundation (T98052).

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Authors and Affiliations

  1. Department of Surgery, Columbia University College of Physicians and Surgeons, 177 Fort Washington Avenue, MHB-7SK 20, New York, New York, 10032

    Kathryn Spanknebel MD, Karl Hurst-Wicker BS, Charles Hesdorffer MD, Gail DeRaffele RN & and Howard L. Kaufman MD

  2. Department of Biostatistics, Columbia University Mailman School of Public Health, 722 West 168th Street, New York, New York, 10032

    Kenneth Y. Cheung PhD

  3. Department of Medicine, Division of Hematology and Oncology, Columbia University College of Physicians and Surgeons, 6 Knuckle Building, Room 435, New York, New York, 10032

    John Stoutenburg MD & Charles Hesdorffer MD

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  1. Kathryn Spanknebel MD
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  2. Kenneth Y. Cheung PhD
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Correspondence to Kathryn Spanknebel MD.

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Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.

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Spanknebel, K., Cheung, K.Y., Stoutenburg, J. et al. Initial Clinical Response Predicts Outcome and Is Associated With Dose Schedule in Metastatic Melanoma and Renal Cell Carcinoma Patients Treated With High-Dose Interleukin 2. Ann Surg Oncol 12, 381–390 (2005). https://doi.org/10.1245/ASO.2005.03.063

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