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. 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. Topotecanproduced 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 fallopian tube adenocarcinoma is of ovarian tissue origin and should be treated as ovarian cancer.
NCCN supports second line use of Avastin alone or in combination – on p. OV-D, 1.
In terms of putting the two drugs together, only one recently completed study addresses this question. Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02).
It concluded that a weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.
McGonigle KF, Muntz HG, Vuky J, Paley PJ, Veljovich DS, Greer BE, Goff BA, Gray HJ, Malpass Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer. 2011 Aug 15;117(16):3731-40.
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.
Burger RA, Brady MF, Bookman MA, et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol. 2010;28:abstract LBA1, ASCO Annual Meeting Proceedings (Post-Meeting Edition). Available at: http://meeting.ascopubs.org/cgi/content/abstract/28/18_suppl/LBA1
Monk B, Han E, Josephs-Cowan C, et al. Salvage Bevacizumab (rhuMAB VEGF)-based Therapy after Multiple Prior Cytotoxic Regimens in Advanced Refractory Epithelial Ovarian Cancer. Gynecologic Oncology. 2006; 102: 140-144.
Robert A. Burger, Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer, Journal of Clinical Oncology, Vol 25, No 20 (July 10), 2007: pp. 2902-2908
Burger R, Brady MF, Bookman MA, et al: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. 2010 ASCO Annual Meeting. Abstract LBA1. Presented June 6, 2010.
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