title: A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer.
abstract: BACKGROUND
  Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open-label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
  
  
  METHODS
  Patients >or= 18 years with a histologic/cytologic diagnosis and no prior chemotherapy for LABC or MBC received pemetrexed 600 mg/m(2) and carboplatin AUC 5.0 on day 1 every 21 days with folic acid and vitamin B(12) supplementation.
  
  
  RESULTS
  From June 2003 to April 2005, 50 patients with stage IIIB (30.0%) and stage IV (70.0%) disease were enrolled at 3 study centers. Twenty-eight percent of patients previously received adjuvant chemotherapy, 46.0% had visceral metastases, and 36.0% had >or=3 organs involved. Partial responses (RECIST criteria) were achieved in 27 (54.0%) patients (ORR = 54.0%; 95% CI, 39.3-68.2%). The median response duration was 11.1 months (95% CI, 6.5-14.0 months) and the median time to disease progression was 10.3 months (95% CI, 8.3-14.6 months). CTC hematologic toxicities were grade 3/4 neutropenia (58.0%/28.0%) and grade 3 thrombocytopenia (10.0%) and anemia (18.0%). Two (4.0%) patients had febrile neutropenia, 1 of whom died. No grade 4 non-hematologic toxicities occurred. Grade 3 non-hematologic toxicities were ALT (4.0%) and AST elevation, and edema, fatigue, pruritus, rash/desquamation, and renal toxicity (2.0% each).
  
  
  CONCLUSIONS
  Results of this study suggest that the combination of pemetrexed and carboplatin has promising efficacy and an acceptable safety profile. Further assessment of this combination in a randomized trial of various breast cancer patient populations is warranted.
authors.affiliation: Russian Cancer Research Center, Moscow, Russian Federation.
authors.forename: August
authors.initials: A
authors.lastname: Garin
authors.forename: Alexey
authors.initials: A
authors.lastname: Manikhas
authors.forename: Mikhail
authors.initials: M
authors.lastname: Biakhov
authors.forename: Mikhail
authors.initials: M
authors.lastname: Chezhin
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ivanchenko
authors.forename: Kurt
authors.initials: K
authors.lastname: Krejcy
authors.forename: Vera
authors.initials: V
authors.lastname: Karaseva
authors.forename: Sergey
authors.initials: S
authors.lastname: Tjulandin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001792:Blood Platelets / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000008:administration & dosage*; D018450:Disease Progression; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068437:Pemetrexed; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin