A Phase 2 Study

BACKGROUND. Dacarbazine (DTIC) and pegylated interferon (IFN)–a-2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors ’ knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial. METHODS. Twenty–eight patients with stage IV melanoma without brain metasta-ses were treated with DTIC (at a dose of 850 mg/m2 every 3 weeks) combined with weekly pegylated IFN–a-2a at a dose of 180 lg. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study end-point was objective response. RESULTS. Twenty–five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for>480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression-free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria). CONCLUSIONS. The combination of DTIC and pegylated IFN–a-2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long-lasting complete responses, is encouraging, but must be con-firmed in larger trials. Cancer 2008;113:1404–11. 2008 American Cancer Society