A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer

Andrea Rocca, Roberta Maltoni, Alessandro Passardi, Ilaria Massa, Michele Aquilina, Ruggero Ridolfi, Toni Ibrahim, Lorenzo Cecconetto, Samanta Sarti, Elisabetta Pietri, Oriana Nanni, Dino Amadori

Research output: Contribution to journalArticle

Abstract

Purpose: Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods: Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results: Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions: The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.

Original languageEnglish
Pages (from-to)871-876
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume65
Issue number5
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Breast cancer
  • Capecitabine
  • Cardiac toxicity
  • Liposomal doxorubicin
  • Phase I dose-finding study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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