Cisplatin + tirapazamine

Cisplatin + tirapazamine is a combination therapy that has been studied primarily for the treatment of non-small-cell lung cancer (NSCLC). This combination pairs cisplatin, a well-established platinum-based chemotherapy agent, with tirapazamine, a novel bioreductive agent that has selective cytotoxicity against hypoxic tumor cells. Tirapazamine represents the first drug from a new class of cytotoxic agents with a unique mechanism of action. It specifically targets hypoxic (low-oxygen) areas of tumors, which are often resistant to conventional treatments. When combined with cisplatin, tirapazamine has demonstrated synergistic effects in preclinical and clinical trials[1][2]. ## Clinical Development In phase I and II clinical trials, the combination has shown promising results. A phase II study involving 44 patients with advanced NSCLC reported a 23% partial response rate and an estimated median survival of 37 weeks[1]. A cumulative analysis of 132 patients with previously untreated, advanced NSCLC showed an objective response rate of 25% with a median survival of 38.9 weeks[2]. The dosing regimen typically consisted of tirapazamine 260 mg/m² administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m² administered over an additional hour, repeated every 21 days[1]. ## Safety Profile The combination therapy has demonstrated a manageable toxicity profile. Common side effects include: - Nausea and vomiting (grade 3 in 25% of patients) - Fatigue (grade 3 in 27.3% of patients) - Muscle cramps (grade 3 in 4.5% of patients) - Gastrointestinal symptoms - Reversible hearing loss (at higher tirapazamine doses of 390 mg/m²) Importantly, tirapazamine does not cause myelosuppression, which is a common dose-limiting toxicity of many chemotherapy regimens. This favorable safety profile allows for effective combination with cisplatin without overlapping dose-limiting toxicities[1][2]. ## Clinical Trials Two large-scale international trials were conducted to further evaluate this combination: 1. CATAPULT I: Compared tirapazamine plus cisplatin with cisplatin alone, with 446 patients enrolled 2. CATAPULT II: Compared tirapazamine plus cisplatin with etoposide plus cisplatin, with 550 patients enrolled by June 1997 These trials aimed to confirm the promising results seen in earlier phase II studies, suggesting that the combination might be more effective than cisplatin monotherapy for advanced NSCLC[2].

Other names

tirapazamine and cisplatin