Phase II evaluation of paclitaxel by short intravenous infusion in metastatic melanoma

In four clinical trials in mostly chemotherapy-naive patients with metastatic melanoma, paclitaxel was found to be effective with a response rate of 16%. In vitro studies have shown that following exposure of cancer cells to paclitaxel for 1 h, sensitivity to repeat paclitaxel doses decreased markedly at 48-72 h and returned at 120 h. In this phase 11 study we assessed the efficacy of paclitaxel at a dose of go mg/m(2) per day given intravenously over 80 min on days 1, 5 and 9 every 3 weeks, initially in two groups of 14 patients with metastatic choroidal and non-choroidal melanoma. One patient in the non-choroidal melanoma group had a confirmed response, and 23 additional patients were therefore accrued to this group. (One patient withdrew consent for treatment within a week from start of therapy. The patient was considered to have received inadequate treatment and a replacement was registered.) A total of 52 patients with a median age of 55 years (range 21-79 years) were treated. Forty-four patients completed two or more courses of paclitaxel and were evaluable for response. We observed >50% tumour regression in six patients. All the responses except one were amongst the 32 evaluable patients with non-choroidal melanoma. The response rate in this group was 15.6%. During the 219 courses of paclitaxel delivered, the side effects were mild, manageable and mostly reversible. No grade 3 acute allergic reactions were observed. Paclitaxel given by short intravenous infusion is marginally active against previously treated non-choroidal melanoma.