Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer

J Clin Oncol. 2004 Oct 1;22(19):3893-901. doi: 10.1200/JCO.2004.08.157.

Abstract

Purpose: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer.

Patients and methods: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m(2) every 28 days); or comparator-vinorelbine (30 mg/m(2) weekly) or mitomycin C (10 mg/m(2) day 1 and every 28 days) plus vinblastine (5 mg/m(2) day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only.

Results: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P =.11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P =.71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P =.01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%).

Conclusion: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Bridged-Ring Compounds / therapeutic use*
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Liposomes
  • Middle Aged
  • Mitomycin / adverse effects
  • Mitomycin / therapeutic use*
  • Neoplasm Metastasis
  • Salvage Therapy
  • Taxoids / therapeutic use*
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use*
  • Vinorelbine

Substances

  • Bridged-Ring Compounds
  • Liposomes
  • Taxoids
  • taxane
  • Mitomycin
  • Vinblastine
  • Doxorubicin
  • Vinorelbine