PHASE-II TRIAL OF TIRAPAZAMINE COMBINED WITH CISPLATIN IN CHEMOTHERAPY OF ADVANCED MALIGNANT-MELANOMA

Purpose: A phase II study was undertaken to determine the efficacy of tirapazamine (TPZ) combined with cisplatin (cDDP) in patients with met astatic melanoma. Patients and methods: Between June 1994 and November 1995, 48 patients with metastatic melanoma were treated with TPZ (260 mg/m(2), administered intravenously over two hours) followed in one-h our by cDDP (75 mg/m(2) over one hour) every 21 days. Sixteen patients had received prior chemotherapy, and 13 of these had failed to respon d to prior cDDP. None of the patients had symptomatic brain metastasis . Results. Nine patients had partial responses, with an overall respon se rate of 19% (95% confidence interval (95% CI) of 9%-33%). The media n duration of response was six months. None of the responders had rece ived prior chemotherapy. Responses were seen in 8 (33%, confidence int erval of 16%-55%) of 24 patients with primary cutaneous melanoma who h ad received no prior chemotherapy and in the only patient with previou sly untreated conjunctival melanoma. There were no responders among th e seven patients with choroidal melanoma and 16 patients with previous ly treated cutaneous melanoma. Two patients with partial responses wer e rendered free of gross disease surgically three months after complet ing eight courses of TPZ-cDDP; they remain free of tumor recurrence. R esponses were seen in lymph nodes (27%), lung (26%), skin (20%), adren al gland (20%); soft tissues (17%) and liver (17%). Common toxicities included muscle cramps, fatigue, gastrointestinal effects and peripher al neuropathy. Fatigue, nausea, vomiting, anorexia: and muscle cramps were grade 3 or 4 in less than 10% of the courses. Neutropenia and thr ombocytopenia were rare. Conclusion: The TPZ-cDDP combination has defi nite activity against chemotherapy-naive patients with cutaneous melan oma and warrant further studies in combination with other cytotoxic ag ents.