Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer

Ann Oncol. 2004 Mar;15(3):440-9. doi: 10.1093/annonc/mdh097.

Abstract

Background: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC).

Patients and methods: Women (n=509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 (every 4 weeks) or doxorubicin 60 mg/m2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose.

Results: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR)=1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR=3.16; 95%CI 1.58-6.31; P<0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR=0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin.

Conclusions: In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / secondary
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Female
  • Heart Diseases / chemically induced
  • Heart Diseases / prevention & control*
  • Humans
  • Liposomes
  • Middle Aged
  • Polyethylene Glycols
  • Prognosis
  • Survival Rate
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Liposomes
  • Polyethylene Glycols
  • Doxorubicin