Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in cutaneous and mucosal metastatic melanoma patients.

Docosahexaenoic acid (DHA)-paclitaxel has a unique pharmacokinetic profile that allows high concentrations of paclitaxel to be delivered to melanoma cells for prolonged periods compared with paclitaxel. We investigated the response rate and safety of weekly DHA-paclitaxel in metastatic melanoma patients. We enrolled chemotherapy-naive patients with metastatic nonchoroidal melanoma using the two-stage Fleming design. At least one response was needed in the first stage to proceed to the second stage. DHA-paclitaxel (500 mg/m2/week by 1-h intravenous infusion) was administered for 5 weeks every 6-week cycle until disease progression, intolerable toxicity, or treatment refusal. Response and toxicity were assessed every 6 weeks and weekly, respectively. Thirty patients were enrolled. The patients' median age was 67 years (range: 29–86 years). The median number of treatment cycles was 2 (range: 1–6 cycles). Three patients (10%) had partial responses; one lasted 4 months, and two lasted 5.6 months. Fifteen patients (50%) had stable disease with a median duration of 2.8 months (range: 2.6–8.9 months). The median survival was 14.8 months. Neutropenia (10%) and musculoskeletal pain (10%) were the most common grade 3 and 4 toxicities, and fatigue (73%), skin rash (70%), and diarrhea (60%) were the most common side effects. As a single-agent therapy, DHA-paclitaxel was well tolerated in metastatic melanoma patients. Its efficacy as a first-line therapy for metastatic melanoma does not exceed that seen with other single-agent chemotherapies such as dacarbazine. Further evaluation of DHA-paclitaxel in combination with other chemotherapy or targeted agents could be considered.