Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer

Ann Oncol. 2012 Dec;23(12):3104-3110. doi: 10.1093/annonc/mds172. Epub 2012 Jul 31.

Abstract

Background: Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer.

Methods: Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS).

Results: Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome.

Conclusion: PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Bridged-Ring Compounds / pharmacology
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / mortality*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality*
  • Platinum / pharmacology
  • Taxoids / pharmacology
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal, Humanized
  • Bridged-Ring Compounds
  • Taxoids
  • taxane
  • Bevacizumab
  • Platinum
  • Doxorubicin