Randomized Phase III Trial of Pegylated Liposomal Doxorubicin Versus Vinorelbine or Mitomycin C Plus Vinblastine in Women With Taxane-Refractory Advanced Breast Cancer
- 1 October 2004
- journal article
- clinical trial
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 22 (19), 3893-3901
- https://doi.org/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/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 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.Keywords
This publication has 13 references indexed in Scilit:
- Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinomaCancer, 2001
- Mitomycin C and Vinblastine in Anthracycline-resistant Metastatic Breast Cancer: A Phase Ii StudyTumori Journal, 2001
- Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus TopotecanJournal of Clinical Oncology, 2001
- Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomesCancer, 1999
- Doxorubicin-Induced CardiomyopathyThe New England Journal of Medicine, 1998
- Polychemotherapy for early breast cancer: an overview of the randomised trialsThe Lancet, 1998
- Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.Journal of Clinical Oncology, 1997
- Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.Journal of Clinical Oncology, 1997
- Polyethylenglykol-umhülltes (pegyliertes) liposomales DoxorubicinDrugs, 1997
- Evaluation of patients with advanced cancer using the karnofsky performance statusCancer, 1980