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. doi: 10.1002/cncr.25967. Epub 2011 Feb 24.

Abstract

Background: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC).

Methods: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity.

Results: 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).

Conclusions: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

Trial registration: ClinicalTrials.gov NCT00343044.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy*
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Peritoneal Neoplasms / drug therapy*
  • Platinum Compounds / pharmacology
  • Topotecan / administration & dosage*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Platinum Compounds
  • Bevacizumab
  • Topotecan

Associated data

  • ClinicalTrials.gov/NCT00343044