title: A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer.
abstract: OBJECTIVE
  Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6.
  
  
  METHODS
  Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m(2)) on day 1, repeated every 2 weeks.
  
  
  RESULTS
  Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %).
  
  
  CONCLUSIONS
  SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted.
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan, k.yamazaki@scchr.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ojima
authors.forename: Toshio
authors.initials: T
authors.lastname: Otsuji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohishi
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002955:Leucovorin; D005472:Fluorouracil