Phase I study of Doxil and vinorelbine in metastatic breast cancer.


Journal Article

BACKGROUND: Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy. PATIENTS AND METHODS: Thirty women with metastatic breast cancer were enrolled. Dose-limiting toxicity was determined through a dose escalation scheme, and defined for the first treatment cycle, only. Pharmacokinetic studies were performed during the first cycle of treatment. RESULTS: In the first cohort of Doxil 30 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8, patients experienced severe neutropenia. Vinorelbine administration was changed thereafter to days 1 and 15 of each cycle. Dose limiting toxicity was observed at Doxil 50 mg/m2 and vinorelbine 25 mg/m2. Doxil 40 mg/m2 and vinorelbine 30 mg/m2 was defined as the maximally tolerated dose. Few toxicities (principally neutro penia) were seen at this dose level, with the notable absence of significant nausea, vomiting, or alopecia. Though 63% of patients had received prior anthracycline-based chemotherapy, only one patient developed grade 2 cardiac toxicity. Pharmacokinetic studies revealed prolonged exposure to high doxorubicin concentrations for several days following Doxil administration. CONCLUSIONS: Combination chemotherapy with Doxil and vinorelbine affords treatment with two active drugs in women with metastatic breast cancer, and appears to have a favorable toxicity profile. A schedule of Doxil 40 mg/m2 day 1 and vinorelbine 30 mg/m2 days 1 and 15 given every 28 days is recommended for phase II studies.

Full Text

Duke Authors

Cited Authors

  • Burstein, HJ; Ramirez, MJ; Petros, WP; Clarke, KD; Warmuth, MA; Marcom, PK; Matulonis, UA; Parker, LM; Harris, LN; Winer, EP

Published Date

  • September 1999

Published In

Volume / Issue

  • 10 / 9

Start / End Page

  • 1113 - 1116

PubMed ID

  • 10572612

Pubmed Central ID

  • 10572612

International Standard Serial Number (ISSN)

  • 0923-7534

Digital Object Identifier (DOI)

  • 10.1023/a:1008323200102


  • eng

Conference Location

  • England