Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy

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/m(2)/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.