title: Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.
abstract: BACKGROUND
  To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines.
  
  
  METHODS
  Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity.
  
  
  RESULTS
  There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%).
  
  
  CONCLUSIONS
  Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.
authors.affiliation: Hospital Universitario San Carlos, Madrid, Spain. mmartin@geicam.org
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: A
authors.initials: A
authors.lastname: duBois
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: D
authors.initials: D
authors.lastname: Dodwell
authors.forename: P
authors.initials: P
authors.lastname: Vodvarka
authors.forename: M
authors.initials: M
authors.lastname: Lind
authors.forename: H
authors.initials: H
authors.lastname: Calvert
authors.forename: A
authors.initials: A
authors.lastname: Casado
authors.forename: L
authors.initials: L
authors.lastname: Zelek
authors.forename: A
authors.initials: A
authors.lastname: Lluch
authors.forename: E
authors.initials: E
authors.lastname: Carrasco
authors.forename: L
authors.initials: L
authors.lastname: Kayitalire
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D000068437:Pemetrexed; D016879:Salvage Therapy; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D004791:Enzyme Inhibitors; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine