title: A phase II study of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA) in patients with unresectable metastatic colorectal cancer.
abstract: OBJECTIVE
  Adding leucovorin to fluorouracil is known to improve response rate and overall survival in first-line chemotherapy for metastatic colorectal cancer (mCRC). The present multicenter phase II study evaluated the efficacy and safety of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA).
  
  
  METHODS
  Patients with unresectable and untreated mCRC received S-1 (40-60 mg bid) plus leucovorin (25 mg bid) orally for 1 week, and oxaliplatin (85 mg/m(2)) and bevacizumab (5 mg/kg) intravenously on day 1, every 2 weeks. Efficacy endpoints, including the response rate (the primary endpoint) and progression-free survival, were assessed by an independent review committee.
  
  
  RESULTS
  Of the 29 eligible patients, 25 patients (86%) had a partial response [95% confidence interval (CI) 68-96%] and the remaining four patients showed stable disease with a trend toward tumor shrinkage. The median progression-free survival was 15 months (95% CI 10-26 months). The median overall survival was not reached after a median follow-up time of 34 months. The 3-year survival rate was 54%. Curative resections of metastatic lesions were performed in eight patients (28%). Common grade 3 or 4 adverse events were neutropenia (20%), hypertension (23%), anorexia (20%), fatigue (17%), diarrhea (10%), and peripheral sensory neuropathy (53%).
  
  
  CONCLUSIONS
  The SOLA therapy showed excellent efficacy and tolerable toxicities except for peripheral sensory neuropathy in patients with mCRC. Since oxaliplatin-induced neuropathy can be alleviated by modifying its administration, SOLA is a promising candidate regimen to be compared with FOLFOX plus bevacizumab in a future phase III trial.
  
  
  BACKGROUND
  JapicCTI-090881.
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Minami Umemoto-machi Kou, Matsuyama, 791-0280, Japan, tnishina@shikoku-cc.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyata
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Moriwaki
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid; D002955:Leucovorin