title: Phase I/II pharmacokinetic study of pemetrexed and epirubicin in patients with locally advanced or metastatic breast cancer.
abstract: BACKGROUND
  Pemetrexed and epirubicin are each active in patients with advanced/metastatic breast cancer (MBC). This phase I/II study evaluated these drugs as a combination regimen.
  
  
  METHODS
  Women with locally advanced or MBC were enrolled. Pemetrexed 400-600 mg/m2 and epirubicin 60-90 mg/m2 were administered on day 1 every 21 days. The recommended phase II dose was evaluated in a 2-stage design.
  
  
  RESULTS
  Phase I enrolled 34 patients and evaluated 5 dose levels. Dose-limiting toxicities were neutropenia and febrile neutropenia. Patients received a median of 7.5 cycles (range, 1-8 cycles), and promising efficacy (partial response [PR], 32%; stable disease [SD], 50%) was observed. Pharmacokinetics of pemetrexed was unchanged when combined with epirubicin. Selected phase II regimen (pemetrexed 600 mg/m2 and epirubicin 75 mg/m2) was administered to 22 patients (median, 4.5 cycles; range 1-13 cycles). Five patients experienced a PR (23%), and 10 experienced SD (46%). This response was below the predefined efficacy requirements for subsequent enrollment, and accrual was stopped. Median time to progression was 5.3 months (95% CI, 3.1-8.9 months), and median time to treatment failure was 3.5 months (95% CI, 2.6-5.9 months).
  
  
  CONCLUSIONS
  The regimen is safe but cannot be recommended as first-line chemotherapy in advanced breast cancer because of the low response rate.
authors.affiliation: Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven, Belgium. robert.paridaens@uz.kuleuven.ac.be
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
authors.forename: Herlinde
authors.initials: H
authors.lastname: Dumez
authors.forename: Annemie
authors.initials: A
authors.lastname: Prové
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
authors.forename: Ana
authors.initials: A
authors.lastname: Alvarez
authors.forename: Celia Tosello
authors.initials: CT
authors.lastname: Oliveira
authors.forename: Jane
authors.initials: J
authors.lastname: Latz
authors.forename: Lorinda
authors.initials: L
authors.lastname: Simms
authors.forename: Allen
authors.initials: A
authors.lastname: Melemed
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068437:Pemetrexed; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D015251:Epirubicin; D006147:Guanine