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Durable Complete Responses With High-Dose Bolus Interleukin-2 in Patients With Metastatic Melanoma Who Have Experienced Progression After Biochemotherapy

Ahmad A. Tarhini, John M. Kirkwood, William E. Gooding, Chao Cai, Sanjiv S. Agarwala

From the University of Pittsburgh Cancer Institute, Pittsburgh; and St Luke’s Hospital and Health Network, Bethlehem, PA

Address reprint requests to Sanjiv S. Agarwala, MD, St Luke's Medical Center, 801 Ostrum St, Bethlehem, PA 18015; e-mail: AgarwaS{at}slhn.edu

Purpose: We conducted a phase II trial of high-dose bolus (HDB) interleukin-2 (IL-2) in patients with metastatic melanoma who had experienced progression after biochemotherapy (BCT).

Patients and Methods: Eligible patients had experienced progression on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2 9 MU/m²/d for 4 days, and interferon alfa-2b). HDB IL-2 was administered at 600,000 U/kg per dose for a maximum of 14 doses per cycle with a 1-week rest period between cycles. Stable or responding patients were offered an additional course (two cycles) after 6 to 8 weeks.

Results: Twenty-six patients (12 men and 14 women), age 28 to 70 years (median, 45 years), have been treated. All but three patients received at least two cycles of HDB IL-2; 10 patients received a second course of therapy. Disease stage was American Joint Committee on Cancer (AJCC) stage M1a (n = 5), M1b (n = 5), and M1c (n = 16). Grade 3 and 4 toxicities included hyperbilirubinemia (n = 10), thrombocytopenia (n = 6), oliguria (n = 3), diarrhea (n = 1), infection (n = 2), and neurologic toxicity (n = 2). Overall response rate was 19.2% (four complete responses, lasting 4, 4, 26+, and 41+ months; and one partial response, lasting 3 months). Five patients (19%) had stable disease lasting 1 to 3 months, but all eventually experienced progression. All four complete responders had AJCC stage M1a disease. At a median follow-up time of 10 months, median survival time was 42 weeks (95% CI, 19.1 to 86.6 weeks), and median progression-free survival time was 10 weeks (95% CI, 8 to 16.1 weeks). An initial response to BCT was not found to be predictive for response to HDB IL-2.

Conclusion: HDB IL-2 is active therapy for patients who experience progression on BCT. This observation has implications regarding the importance of dose-intensity for IL-2 therapy.

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

Related Editorial

• More Support for the Judicious Use of High-Dose Interleukin-2 in Patients With Advanced Melanoma
  David F. McDermott and Michael B. Atkins
  JCO 2007 25: 3791-3793 [Full Text]

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