Phase II study of temozolomide plus pegylated interferon-α-2b for metastatic melanoma

BACKGROUND. Temozolomide and interferon-α-2b (IFN-α-2b) are both active in melanoma. Therefore, the efficacy and safety of temozolomide in combination with pegylated IFN-α-2b in patients with metastatic melanoma without brain metastases was investigated. METHODS. Patients with histologically confirmed, unresectable, American Joint Committee on Cancer Stage FV melanoma were enrolled in an open-label, Phase II study. The primary endpoints were tumor response and safety. Patients received temozolomide (75 mg/m²/day × 6 weeks with a 2-week break between cycles) plus concomitant subcutaneous pegylated IFN-α-2b (0.5 μg/kg/wk, continuously). Treatment was continued until unacceptable toxicity or disease progression occurred. RESULTS. Thirty-five patients (median age, 55 years) with Stage IV melanoma and a median of 3 metastatic sites were enrolled and received a median of 1 cycle (i.e., 8 weeks) of therapy (range, 0-6 cycles). Eleven patients (31%) (95% confidence interval, 16% to 47%) had an objective tumor response, including 3 with clinical complete response durations of 6 months, 20 months, and 32+ months and 8 with partial responses. Three patients with a partial or mixed response were subsequently rendered free of clinically detectable disease with surgery. The median survival was 12 months with a median follow-up among survivors of 16 months. No patient developed brain metastases while receiving study treatment. Treatment was generally well tolerated. Hematologic toxicity consisted mainly of lymphopenia and leukopenia (National Cancer Institute Common Toxicity Criteria Grades 1-3); no Grade 4 hematologic toxicity was observed. CONCLUSIONS. The combination of temozolomide plus pegylated IFN-α-2b had antitumor activity and was well tolerated in patients with metastatic melanoma. Therefore, further study is warranted.