[Topoisomerase I inhibitor with potential radiosensitizing effect].

AIM: In search of new drugs which should be theoretically able to modify radiation effects, the topoisomerase I-inhibitor topotecan was identified in November 1996, approval for second-line therapy of ovarian carcinoma was given in Germany. MATERIAL AND
METHOD: This review article describes mechanisms of action, pharmacokinetic, preclinical and recent clinical data on topotecan with and without concomitant radiation therapy.
RESULTS: Following a 30 min. intravenous bolus, median plasma half-lives between 2 and 3 h. and a total-body clearance of 0.57 l/min/m2 were seen. After oral administration the bioavailability varied between 30 and 35%. Topotecan is able to pass the blood brain barrier. Encouraging clinical results are reported in gastrointestinal tumors, head and neck squamous cell carcinoma, small cell and non-small cell lung cancer, breast cancer, leukemia and pediatric tumors in addition to ovarian carcinoma. Recent studies indicate that topotecan functions as a radiosensitizer and may be applied together with radiation in future trials. In vivo and in vitro experiments revealed a good modulation ofradiation effects of topotecan.
CONCLUSIONS: In experimental and preclinical studies using topotecan both additive and sensitization effects to normal cells and tumor cells were seen by ionizing radiation. Clinical phase II/III trials may preferentially be indicated in non-small cell lung cancer and primary and metastatic brain tumors.