title: A Phase II Study of Third-Line Combination Chemotherapy with Bevacizumab Plus S-1 for Metastatic Colorectal Cancer with Mutated KRAS (SAVIOR Study).
abstract: OBJECTIVE
  No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC.
  
  
  METHODS
  Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR).
  
  
  RESULTS
  In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progression-free survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥3, 17%).
  
  
  CONCLUSIONS
  The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS.
authors.affiliation: Cancer Chemotherapy Center, Osaka Medical College Hospital, Osaka, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Akinori
authors.initials: A
authors.lastname: Takagane
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ogata
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Koki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kagimura
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016879:Salvage Therapy / Q000379:methods; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C117307:KRAS protein, human; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid; D016283:Proto-Oncogene Proteins p21(ras)