title: Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur-gimeracil-oteracil potassium in metastatic and recurrent breast cancer.
abstract: BACKGROUND
  We investigated the efficacy and safety of metronomic chemotherapy with combined irinotecan and tegafur-gimeracil-oteracil potassium (TS-1) in patients with metastatic and recurrent breast cancer (MRBC), and the association between irinotecan metabolizing enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms and adverse events.
  
  
  METHODS
  The study group comprised 40 patients aged 35-79 years. Irinotecan (60 mg/m(2) in 5 % dextrose) was administered by 120-min infusion on days 1, 8, and 15 every 4 weeks. TS-1 (prescribed in a standard quantity) was administered at 80 mg/m(2)/day orally on days 3-7, 10-14, and 17-21 every 4 weeks.
  
  
  RESULTS
  Tumor response data were available for 34 patients. Median follow-up was 12 months (range 1-45 months). Response rate was 47 % (one complete and 15 partial responses). Stable disease was observed in 17 patients (50 %). One patient had disease progression (3 %). Median progression-free survival was 14 months [95 % confidence interval (CI), 10-26]. Median overall survival was 26 months (95 % CI not calculable owing to sample size), and 79.3 % of patients survived for 1 year. The most common grade 3 or 4 adverse events were neutropenia (15 %), leukopenia (12.5 %), diarrhea (7.5 %), and anemia (2.5 %). All other adverse events were grade 1 or 2. Treatment-related toxicity was generally modest and manageable. No significant correlation was observed between UGT1A1 polymorphisms and hematological or non-hematological toxicities.
  
  
  CONCLUSIONS
  Metronomic chemotherapy with combined irinotecan and TS-1 was effective in MRBC patients. Adverse effects were mild and the regimen was safely administered without identifying UGT1A1 polymorphisms.
authors.affiliation: Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otsuka
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Iwakuma
authors.forename: Ryuji
authors.initials: R
authors.lastname: Takahashi
authors.forename: Mai
authors.initials: M
authors.lastname: Mishima
authors.forename: Miki
authors.initials: M
authors.lastname: Takenaka
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kakuma
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000008:administration & dosage; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D004338:Drug Combinations; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D010094:Oxonic Acid; D011725:Pyridines; D005641:Tegafur; D000099148:UGT1A1 Enzyme; C586502:tegafur-gimeracil-oteracil