Topotecan is a water-soluble, semisynthetic analogueof camptothecin that inhibits the nuclear enzyme topoisomeraseI. Topotecan has been approved by the U.S. Food and DrugAdministration (FDA) for the treatment of recurrent epithelialovarian cancer and relapsed small cell lung cancer,and has also demonstrated activity in hematologic malignancies and solid tumors including non-small cell lung, cervical, and colon cancers. It is no longer experimental.
In ovariancancer, topotecan has demonstrated activity in both platinum-and paclitaxel-resistant tumors, with response rates rangingfrom 12%-33%. In a randomized, phase III study,ovarian cancer patients showed similar response rates with topotecan(21%; n = 112) and paclitaxel (13%; n = 114; p = 0.138) Approximately half of all patients in both arms of thestudy had progressed on a platinum-based regimen or had relapsedwithin 6 months of completing first-line therapy. Topotecan produced responses in 8 of 61 (13%) patients in whom paclitaxelhad failed to produce a response. Similarly, paclitaxel producedresponses in 5 of 49 (10%) patients in whom topotecan had failedto produce a response. That phase III study, and earlierphase II studies, established topotecan as an important treatment option for patients with either platinum-sensitive or platinum-refractoryrelapsed ovarian cancer. NCCN lists it as well as level 2b recommendation.It is generally assumed that primary peritoneal serous adenocarcinoma is of ovarian tissue origin and should be treated as ovarian cancer.
Bookman MA, Malmstrom H, Bolis G et al. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol 1998;16:3345–3352.
Miller DS, Blessing JA, Lentz SS et al. Phase II evaluation of three-day topotecan in recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study. Presented at the 33rd Annual Meeting of the Society of Gynecologic Oncologists, Miami, FL, March 16–20, 2002.