title: A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study.
abstract: OBJECTIVE
  This phase II study was undertaken to define the efficacy and toxicity of pemetrexed in combination with gemcitabine in patients with metastatic breast cancer.
  
  
  METHODS
  Patients with measurable metastatic breast cancer who had previously received an anthracycline and a taxane in either the adjuvant or metastatic setting were treated with gemcitabine 1250 mg/m2 (intravenous; days 1 and 8) and pemetrexed 500 mg/m2 (intravenous; day 8) every 21 days.
  
  
  RESULTS
  Fifty-nine patients received a median of five cycles (range one to 22) of treatment and were followed until death or for a median of 28 months (range 19.4-36.6) among living patients. Fourteen partial responses for an overall response rate of 24% [95% confidence interval (CI) 16% to 39%] were documented. Nine (15%; CI 5% to 32%) patients had stable disease for >6 months. The median survival time was 10.3 months (95% CI 8.3-18.9) and the 1 year survival rate was 49% (95% CI 38% to 64%). The median time to progression was estimated to be 3.7 months (95% CI 2.3-5.3). The most common grade 3 or 4 toxicities were neutropenia and thrombocytopenia in 83% and 27% of patients, respectively. Fourteen percent of patients experienced febrile neutropenia. Other common grade 3 or 4 non-hematological toxicities included fatigue (17%), dyspnea (15%), rash (7%) and anorexia (5%).
  
  
  CONCLUSIONS
  The combination of pemetrexed and gemcitabine is clinically active, with an overall response rate of 24% in patients with metastatic breast cancer who have previously been treated with an anthracycline and a taxane. Myelosuppression (66% grade 4 neutropenia and 14% febrile neutropenia) was the major treatment-related toxicity observed for this combination.
authors.affiliation: Mayo Clinic and Foundation, Department of Oncology and Medicine, Rochester, MN 55905, USA.
authors.forename: C X
authors.initials: CX
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Steen
authors.forename: K M
authors.initials: KM
authors.lastname: Rowland
authors.forename: R D
authors.initials: RD
authors.lastname: Niedringhaus
authors.forename: T R
authors.initials: TR
authors.lastname: Fitch
authors.forename: J W
authors.initials: JW
authors.lastname: Kugler
authors.forename: D W
authors.initials: DW
authors.lastname: Hillman
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.forename: A A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine