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 cisp latin in preclinical testing. This phase II study was conducted to eva luate the efficacy and toxicity of tirapazamine with cisplatin in pati ents with advanced non-small-cell lung cancer. Patients and methods: T wenty patients with unresectable stage III-B and IV non-small-cell lun g cancer who had not received prior chemotherapy were given tirapazami ne (390 mg/m(2)) intravenously (i.v.) over two hours followed one hour later by cisplatin (75 mg/m(2)) i.v. over one hour every 21 days. Res ults. Five of 20 patients (25%) had major objective responses (95% con fidence interval, 11%-50%). Median duration of response was eight mont hs with a one-year survival of 40%. Toxicities included temporary hear ing loss (25%), muscle cramping, diarrhea, skin rash and nausea/vomiti ng. No grade 3 or 4 hematologic or renal toxicity was observed. Conclu sions. The combination of tirapazamine plus cisplatin appears to be sa fe and active in the treatment of advanced non-small lung cancer witho ut a substantial increase in toxicity compared to cisplatin alone. A p hase III randomized study comparing the combination to cisplatin alone has completed accrual. Further evaluation of tirapazamine with other active agents and in multi-modality therapy is warranted.