title: A phase I/II study of XELIRI plus bevacizumab as second-line chemotherapy for Japanese patients with metastatic colorectal cancer (BIX study).
abstract: BACKGROUND
  Capecitabine is used mainly with oxaliplatin to treat metastatic colorectal cancer (mCRC). Results from capecitabine plus irinotecan (XELIRI) with or without bevacizumab (BV) have been reported in Europe but not in Japan. Consequently, the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC were assessed in a single-arm phase II study.
  
  
  METHODS
  Eligible patients had had prior chemotherapy containing BV for mCRC and wild-type or heterozygous UGT1A1. Therapy in each 21-day treatment cycle consisted of capecitabine (800 mg/m(2) twice daily on days 1-15), irinotecan (200 mg/m(2) on day 1), and BV (7.5 mg/kg on day 1). The primary endpoint was dose-limiting toxicity in phase I and progression-free survival (PFS) in phase II.
  
  
  RESULTS
  A total of 34 patients (6 in phase I, 28 in phase II) were enrolled from May 2010 to June 2011. Baseline characteristics included a median age of 60 years (range: 22-74 years) for 24 men and 10 women. No dose-limiting toxicities appeared in phase I. Median PFS was 240 days (95% confidence interval: 179-311 days). Overall response rate was 18.1%, and the disease-control rate was 90.9%. The incidence of adverse events frequently associated with irinotecan and capecitabine were neutropenia (any grade, 55.9%; grade 3 or 4, 11.8%), diarrhea (any grade, 50%; grade 3 or 4, 5.9%), and hand-foot syndrome (any grade, 61.8%; grade 3 or 4, 5.9%).
  
  
  CONCLUSIONS
  Our results suggest that XELIRI plus BV is well tolerated and effective as a second-line treatment for mCRC in Japanese patients. This regimen could be especially appropriate for patients resistant to oxaliplatin-based regimens.
authors.affiliation: Keio Cancer Center, School of Medicine, Keio University, Tokyo, Japan; yhamamoto@z2.keio.jp yayamada@ncc.go.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamoto
authors.affiliation: Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan;
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan;
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan;
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Central Hospital, Nagoya, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.affiliation: Department of Medical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan;
authors.forename: Takako
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Clinical Oncology, Yokohama City University Hospital, Kanagawa, Japan;
authors.forename: Ayumu
authors.initials: A
authors.lastname: Goto
authors.affiliation: Department of Medical Oncology, Showa University Northern Yokohama Hospital, Kanagawa, Japan;
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center Hospital, Kanagawa, Japan;
authors.forename: Norisuke
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Director, Tokai Central Hospital, Gifu, Japan;
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Biostatistics and Epidemiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan yhamamoto@z2.keio.jp yayamada@ncc.go.jp.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin