title: Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer.
abstract: OBJECTIVE
  Metronomic combination chemotherapy with the oral fluoropyrimidine doxifluridine/5'-deoxy-5-fluorouridine (5 -DFUR) and oral cyclophosphamide (C) showed promising efficacy in a single-arm study. The oral fluoropyrimidine capecitabine was designed to deliver 5-fluorouracil preferentially to tumors, potentially improving efficacy over doxifluridine. We conducted a phase II multicenter study to evaluate an all-oral XC combination in patients with HER2-negative metastatic breast cancer (MBC).
  
  
  METHODS
  Patients received capecitabine 828 mg/m(2) twice daily with cyclophosphamide 33 mg/m(2) twice daily, days 1-14 every 3 weeks. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
  
  
  RESULTS
  Between May 2007 and April 2009, 51 patients were enrolled and 45 were included in the efficacy analysis. The median follow-up was 18.1 months. ORR was 44.4% and stable disease (≥24 weeks) was achieved in 13.4%, resulting in a 57.8% clinical benefit response rate. Median PFS was 12.3 months (95% confidence interval: 8.9-18.9 months). Median PFS was 10.7 months in triple-negative disease and 13.2 months in estrogen-receptor positive, HER2-negative disease. The 1- and 2-year OS rates were 86 and 71%, respectively. Median OS has not been reached. Grade 3 adverse events comprised leukopenia (26%), neutropenia (16%), and decreased hemoglobin (2%). There was no grade 3 hand-foot syndrome.
  
  
  CONCLUSIONS
  Oral XC is an effective first- or second-line therapy for MBC, demonstrating high activity in both luminal A and triple-negative disease with few severe side effects. This metronomic oral combination chemotherapy could be beneficial for the treatment of HER2-negative MBC.
authors.affiliation: Breast Center, Mita Hospital, International University of Health and Welfare, Minato-ku, Tokyo 108-8329, Japan. yoshimoto@yoshimoto-bc.com
authors.forename: Masataka
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takao
authors.forename: Masaru
authors.initials: M
authors.lastname: Hirata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Sumio
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Takami
authors.forename: Hidemi
authors.initials: H
authors.lastname: Furusawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Chigusa
authors.initials: C
authors.lastname: Abe
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human