title: A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD).
  
  
  RESULTS
  Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively.
  
  
  CONCLUSIONS
  XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohnuma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osuga
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okagawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Murase
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin