Phase II trial of high-dose bolus IL-2 in patients with metastatic melanoma (mm) who have previously failed biochemotherapy (BCT)

Abstract

7512 Background: BCT comprising combination chemotherapy, infusional IL-2 and IFN-alfa has produced high response rates (40–50%) in phase II studies, but recent randomized trials have failed to show a superiority for BCT over CT alone. High-dose bolus (HDB) IL-2 can produce long-term remissions in 6–10% of previously untreated patients with MM and utilizes considerably higher doses of IL-2, raising the question of whether HDB IL-2 may have activity in patients who have progressed following BCT. Methods: A phase II trial of HDB IL-2 for patients who had progressed following BCT was conducted at the University of Pittsburgh. Eligible patients had measurable disease, PS 0–1 and had progressed on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2, 9 MU/m2/day × 4 days, and IFN-alfa 2b). HDB IL-2 was administered at 600,000 U/kg per dose, for a maximum of 14 doses per cycle with a one-week rest period between cycles. Stable or responding patients were offered an additional course of therapy after 6–8 weeks. Treatment was conducted on an in-patient oncology unit with trained personnel. Results: To date, 26 patients (12 male, 14 female) age 26–70 (median 44) years have been treated. All but 3 patients received at least two cycles (one course) of HDB IL-2; 10 patients recieved a second course of therapy. The median number of doses administered was 9 (range 6–14) during cycle 1 and 7 (range 2–12) during cycle 2. Disease stage was AJCC Mla (5) Mlb (5) and Mlc (16). Grade 3 toxicities included hyperbilirubinemia (10), thrombocytopenia (6), tachycardia (5), hypotension (4), oliguria (3), diarrhea (1), infection (2) and neurologic (2). Grade 4 toxicities included thrombocytopenia (1) and hyperbilirubinemia (1). Overall response rate was 19% (4 complete, 1asting 4, 4, 5 and 12+ months, 1 partial, lasting 3 months). Seven patients (27%) had SD lasting 1–3 months, but all eventually progressed. All 4 complete responders were AJCC Stage Mla. Median survival is 26.4 weeks for the entire group (95% CI 11.4–57.6 weeks). Conclusions: HDB IL-2 is active in patients with MM who progress on BCT, an observation that has implications for dose intensity with this agent. No significant financial relationships to disclose.