title: Phase I study of Doxil and vinorelbine in metastatic breast cancer.
abstract: BACKGROUND
  Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy.
  
  
  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.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramirez
authors.forename: W P
authors.initials: WP
authors.lastname: Petros
authors.forename: K D
authors.initials: KD
authors.lastname: Clarke
authors.forename: M A
authors.initials: MA
authors.lastname: Warmuth
authors.forename: P K
authors.initials: PK
authors.lastname: Marcom
authors.forename: U A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: L M
authors.initials: LM
authors.lastname: Parker
authors.forename: L N
authors.initials: LN
authors.lastname: Harris
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013997:Time Factors; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine