Key role of topoisomerase I inhibitors in the treatment of recurrent and refractory epithelial ovarian carcinoma.
Ovarian cancer remains one of the most difficult gynecologic cancers to treat, owing to its aggressive biology and high relapse rate, as well as the toxic side effects of available chemotherapeutic agents used to treat recurrent disease. Topoisomerase I inhibitors, including topotecan and irinotecan, are some of the most effective and tolerable treatment options for recurrent ovarian cancer. The ideal dosing, timing of administration, role in combination with other chemotherapies or biologics and potential role in up-front therapy remains an area of active research. This article reviews the mechanism of action of topoisomerase I inhibitors and the efficacy, dosing, schedule and toxicity for topotecan, irinotecan, 9-nitrocamptothecin, DX-8951 and 9-aminocamptothecin. Conclusions include a discussion of future avenues of research and ongoing projects.
Wethington
Stephanie L
SL
Columbia University College of Physician and Surgeons, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, 161 Fort Washington Ave, 8th Floor, Room 838, New York, NY 10032, USA. slw2004@columbia.edu
Wright
Jason D
JD
Herzog
Thomas J
TJ
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C080125:9-aminocamptothecin; D000077146:Irinotecan; D019772:Topotecan; C079905:rubitecan; C095887:exatecan; D002166:Camptothecin