Phase II study of the combination of the novel bioreductive agent, tirapazamine, with cisplatin in patients with advanced non-small-cell lung cancer.
PURPOSE: Tirapazamine is a bioreductive compound synergistic with cisplatin in preclinical testing. This phase II study was conducted to evaluate the efficacy and toxicity of tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: Twenty patients with unresectable stage III-B and IV non-small-cell lung cancer who had not received prior chemotherapy were given tirapazamine (390 mg/m2) intravenously (i.v.) over two hours followed one hour later by cisplatin (75 mg/m2) i.v. over one hour every 21 days. RESULTS: Five of 20 patients (25%) had major objective responses (95% confidence interval, 11%-50%). Median duration of response was eight months with a one-year survival of 40%. Toxicities included temporary hearing loss (25%), muscle cramping, diarrhea, skin rash and nausea/vomiting. No grade 3 or 4 hematologic or renal toxicity was observed. CONCLUSIONS: The combination of tirapazamine plus cisplatin appears to be safe and active in the treatment of advanced non-small lung cancer without a substantial increase in toxicity compared to cisplatin alone. A phase III randomized study compared the combination to cisplatin alone has completed accrual. Further evaluation of tirapazamine with other active agents and in multi-modality therapy is warranted.