title: Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab.
abstract: Fluorouracil and folinic acid with irinotecan (FOLFIRI) plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, oxaliplatin, and BV. FOLFIRI requires a CV catheter and an infusion pump, which are inconvenient for patients. Sufficient data are not available for characterizing the effectiveness of fluoropyrimidines beyond first disease progression. In this study, we evaluated the efficacy and safety of irinotecan (CPT-11) plus BV as second-line therapy.
  
  
  
  Patients with mCRC previously treated with at least four courses of a fluoropyrimidine, oxaliplatin, and BV were designated to receive 150 mg/m2of CPT-11 and 10 mg/kg of BV every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events.
  
  
  
  Thirty patients from six institutes were enrolled from March 2011 to January 2014. The median PFS was 5.7 months (95% CI 4.2-7.3 months), and the RR was 6.7% (range 0.8-22.1%). Grades 3-4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5 and 96.3% for CPT-11 and BV, respectively. The median OS was 11.8 months (6.3 months-not reached).
  
  
  
  Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacies with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged as satisfactory.
  
  
  
  UMIN000005228.
authors.affiliation: Department of Surgery, Yachiyo Medical Center, Tokyo Women's Medical University, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan. kuramochi.hidekazu@twmu.ac.jp.|Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan. kuramochi.hidekazu@twmu.ac.jp.|Tsukuba Gastrointestinal Hospital, 1-2-39, Takamihara, Tsukuba, Ibaraki, Japan. kuramochi.hidekazu@twmu.ac.jp.
authors.forename: Hidekazu
authors.identifier: 0000-0003-0875-7393
authors.initials: H
authors.lastname: Kuramochi
authors.affiliation: Department of Surgery, Toshima Metropolitan Hospital, 33-1, Sakaecho, Itabashiku, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Surgery II, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Itabashi
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Nakajima
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Surgery, Yachiyo Medical Center, Tokyo Women's Medical University, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Hamano
authors.affiliation: Department of Surgery, Yachiyo Medical Center, Tokyo Women's Medical University, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hirai
authors.affiliation: Department of Surgery, Medical Center East, Tokyo Women's Medical University, 2-1-10, Nishioku, Arakawaku, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yokomizo
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Okuyama
authors.affiliation: Department of Surgery, Yachiyo Medical Center, Tokyo Women's Medical University, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Araida
authors.affiliation: Department of Surgery, Medical Center East, Tokyo Women's Medical University, 2-1-10, Nishioku, Arakawaku, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshimatsu
authors.affiliation: Department of Surgery II, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kameoka
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjukuku, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Bevacizumab; Colorectal cancer; Irinotecan (CPT-11); Second-line