[Topoisomerase I inhibitor with potential radiosensitizing effect].
OBJECTIVE
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.


METHODS
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.
Sauer
R
R
Klinik und Poliklinik für Strahlentherapie, Universität Erlangen-Nürnberg.
Heuser
A
A
D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002648:Child; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D059004:Topoisomerase I Inhibitors; D019772:Topotecan
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D002166:Camptothecin