Biweekly Pegylated Liposomal Doxorubicin (Caelyx) in Heavily Pretreated Metastatic Breast Cancer: A Phase 2 Study

Clin Breast Cancer. 2016 Dec;16(6):514-519. doi: 10.1016/j.clbc.2016.06.001. Epub 2016 Jun 14.

Abstract

Background: Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen.

Patients and methods: A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m2) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m2. Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine.

Results: The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand-foot syndrome. The low rate of hematologic toxicity and hand-foot syndrome is clinically noteworthy.

Conclusion: Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients.

Keywords: Advanced breast cancer; Anthracyclines; Pegylated liposomal doxorubicin (PLD); Phase II Trial.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / therapeutic use
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Capecitabine / therapeutic use
  • Cardiotoxicity / epidemiology
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Drug Administration Schedule
  • Female
  • Hand-Foot Syndrome / epidemiology
  • Hand-Foot Syndrome / etiology
  • Humans
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Taxoids / therapeutic use
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / epidemiology
  • Treatment Outcome
  • Vinblastine / analogs & derivatives
  • Vinblastine / therapeutic use
  • Vinorelbine

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Taxoids
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Vinblastine
  • Capecitabine
  • Doxorubicin
  • Vinorelbine