Topotecan in the management of cervical cancer

Topotecan, a semisynthetic camptothecin, exerts its cytotoxic effect through inhibition of DNA topoisomerase I. Single-agent topotecan has demonstrated activity against persistent, metastatic and recurrent cancer of the uterine cervix. When combined with cisplatin in Phase II trials, further improved response rates have been reported. The cisplatin/topotecan doublet subsequently proved to be the first regimen in a series of multiple Phase III studies to demonstrate improved disease-free and overall survival in this setting compared with cisplatin alone, thus leading to its third indication by both the US FDA and the European Medicines Agency in 2006. This survival advantage was achieved at the expense of an increase in grade 3-4 hematologic toxicity; however, there was no difference in patient-reported quality of life between the cisplatin/topotecan doublet and single-agent cisplatin. This article reviews the pharmacology of topotecan and its evolution as an active agent in advanced and metastatic cervical cancer that is not amenable to cure with surgery or radiotherapy.