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Tirapazamine-cisplatin: the synergy
U Gatzemeier1, G Rodriguez, J Treat
1Department of Thoracic Oncology, Hospital Grosshansdorf, Hamburg, Germany.
British Journal of Cancer
|July 1, 1998
Summary
Tirapazamine, a novel bioreductive agent, shows promise in treating advanced non-small-cell lung cancer (NSCLC) when combined with cisplatin. This combination demonstrated improved efficacy and a manageable safety profile in clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Tirapazamine is a novel bioreductive agent with selective cytotoxicity against hypoxic tumor cells.
- Preclinical studies indicated synergy between tirapazamine and cisplatin, suggesting potential in cancer treatment.
Purpose of the Study:
- To evaluate the safety and efficacy of tirapazamine in combination with cisplatin for advanced non-small-cell lung cancer (NSCLC).
- To assess the pharmacokinetic profile and dose-limiting toxicities of tirapazamine.
Main Methods:
- Phase I trial with escalating doses of tirapazamine and cisplatin.
- Three Phase II trials in advanced NSCLC patients.
- Pharmacokinetic studies and analysis of adverse events.
- Intent-to-treat analysis of 132 patients for anti-tumor efficacy.
Main Results:
- Limiting toxicity was acute, reversible hearing loss at 390 mg m(-2); other side effects included muscle cramping and GI symptoms.
- No myelosuppression or toxic deaths were reported.
- Objective response rate was 25% with a median survival of 38.9 weeks in advanced NSCLC patients.
- Efficacy of tirapazamine plus cisplatin was superior to historical cisplatin monotherapy controls.
Conclusions:
- Tirapazamine is a promising agent from a new class of cytotoxic drugs with a novel mechanism of action.
- The combination of tirapazamine and cisplatin is safe and effective for NSCLC treatment due to its safety profile and lack of overlapping toxicities.
- Ongoing large-scale international trials (CATAPULT I and II) are confirming these findings.