title: S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102).
abstract: Combination chemotherapy with S-1 and irinotecan is one of the standard treatments for metastatic colorectal cancer (mCRC) in Japan. However, there are few alternative practical second-line therapies. We conducted a phase II trial to evaluate the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab as a second-line treatment for oxaliplatin-refractory mCRC.
  
  
  
  Patients with mCRC who were previously treated with oxaliplatin-containing regimens were enrolled. Oral S-1 at a dose of 40 mg/m(2) was administered twice daily for 2 weeks, followed by a 1-week drug-free interval. Irinotecan at a dose of 150 mg/m(2) and bevacizumab at a dose of 7.5 mg/kg were administered on day 1. The primary endpoint was progression-free survival (PFS).
  
  
  
  Thirty-seven patients were enrolled, and 34 and 36 patients were assessed for response and safety, respectively. The overall response rate was 20.6 % (95 % confidence interval [CI] 8.7-37.9), and the disease control rate was 76.5 % (95 % CI 58.8-89.3). The median PFS was 5.6 months (95 % CI 3.8-7.0). The median overall survival was 16.4 months (95 % CI 8.1-20.0). The most common grade 3/4 adverse events included neutropenia (25.0 %), anorexia (22.2 %), anemia (16.7 %), and fatigue/malaise (16.7 %). The most common grade 3/4 adverse event of special interest for bevacizumab was hypertension (30.6 %). One treatment-related death caused by gastrointestinal bleeding occurred.
  
  
  
  The findings suggest that the combination of S-1 and irinotecan plus bevacizumab is effective and tolerable as second-line chemotherapy for patients with oxaliplatin-refractory mCRC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Medical Oncology, Okayama Rousai Hospital, Okayama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanioka
authors.affiliation: Department of Surgery, Munakata Medical Association Hospital, Fukuoka, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Maekawa
authors.affiliation: National Hospital Organization, Beppu Medical Center, Beppu, Japan.|Clinical Research Institute and Department of Surgery, Oita, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawanaka
authors.affiliation: Gastroenterological Surgery, Nanpuh Hospital, Kagoshima, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitazono
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Emi
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Department of Surgery, Kurume University Medical Center, Kurume, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Gastroenterological Surgery, Nanpuh Hospital, Kagoshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Cancer Information Research, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Shimokawa
authors.affiliation: Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin
keywords: Bevacizumab; Chemotherapy; Colorectal cancer; Irinotecan; S-1