Background: Previous biochemotherapy regimens for metastatic melanoma have required attenuated dosages of interleukin 2 (IL-2) that may have compromised efficacy.
Methods: In a phase 2 study, the authors tested sequential temozolomide (75 mg/m2 per day orally for 3 weeks) followed by high-dose, IL-2 (600,000 U/kg per dose intravenously; maximum, 14 doses over 5 days).
Results: Thirty-eight patients with treatment-naive American Joint Committee on Cancer stage IV melanoma (8 patients with M1a disease, 6 patients with M1b disease, and 24 patients with M1c disease) were enrolled. Ten patients had a history of treated brain metastases. Thirty-one patients who received at least 2 cycles of IL-2 were evaluable for response. Grade 3 toxicities included hyperbilirubinemia (9 patients), hematologic toxicities (leukopenia in 5 patients, thrombocytopenia in 3 patients), diarrhea (2 patients), and oliguria (1 patient). One patient had grade 4 nausea. The overall response rate (ORR) was 16% and included 3 complete responses that lasted 10.8 months, > or =32 months, and > or =36 months and 2 partial responses that lasted 13 months and 14 months. Responses were observed in patients with M1a disease and in patients with M1c disease. Sixteen patients had stable disease (15 patients progressed). The median progression-free survival (PFS) was 5.3 months (95% confidence interval [CI], 3.7-7.5 months). The probability of PFS at 6 months was 0.52 (95% CI, 0.33-0.67). Among 38 enrolled patients, 16 patients remained alive at a median follow-up of 6.7 months (range, 1.9-36.1 months). The median overall survival (OS) was 12.1 months (95% CI, 9.1-16.4 months), and the probability of 12-month OS was 0.54 (95% CI, 0.34-0.70 months).
Conclusions: The current results indicated that it is safe to administer HD IL-2 sequentially with temozolomide and that this combination has lower toxicity than previously used concurrent biochemotherapy regimens. However, The ORR and the durability of responses with this combination did not exceed those of single-agent HD IL-2.