title: Initial Report of Phase II Study on Bi-weekly SOX plus Cetuximab Treatment for Wild-type K-RAS Advanced and Recurrent Colorectal Cancer.
abstract: OBJECTIVE
  This prospective study was designed to evaluate the tolerability and the efficacy of bi-weekly SOX (S-1 and oxaliplatin)+cetuximab as first-line chemotherapy for wild-type K-RAS metastatic colorectal cancer.
  
  
  METHODS
  We studied patients with previously untreated, unresectable, advanced or recurrent colorectal cancer who were treated in our hospital between October 2010 and March 2013. Their performance status (PS) was 0 to 1. Cetuximab was combined with S-1 and oxaliplatin (SOX+cetuximab). S-1 was given orally at a dose of 40 mg/m(2) (40-60 mg, calculated according to body surface area) twice daily after meals for 2 weeks, followed by a 2-week rest (course 1). Oxaliplatin (85 mg/m(2)) was given on days 1 and 15 of each course. Cetuximab was administered on days 1 (400 mg/m(2)), 8 (250 mg/m(2)) and 15 (500 mg/m(2)) of course 1, followed by every 2 weeks (500 mg/m(2)) thereafter.
  
  
  RESULTS
  The study group comprised of 18 patients. The mean age was 61 (range=32-72) years, the male:female ratio was 10:8 and the PS was 0 in 12 patients and 1 in 6 patients. The median number of administered courses was 6 (range=2-12). The treatment response was complete response (CR) in 2 and partial response (PR) in 10 (response rate=67% (12/18 patients)). The minimum number of treatment courses until a PR was 2, indicating an early response. Liver resection was performed in 4 patients (22.2%). The incidence of any adverse events (Grade 3/4) was 28% (5/18), including skin disorder (16.7%) as dry skin, cutaneous pruritus, contusion and paronychia, as well as peripheral sensory neuropathy (11.1%). The any-grade events of skin disorders and peripheral sensory neuropathy were mostly observed in all patients. These events were controllable by preventive skin care and by withdrawal and dose reduction, respectively. Death due to adverse events was not observed. Adverse events did not require the withdrawal of this regimen.
  
  
  CONCLUSIONS
  Based on the 18 patients studied, combined therapy with SOX+cetuximab was free of serious adverse events and could be safely administered by reducing the dose or temporarily suspending treatment, as required. These regimens seem to be promising for conversion therapy (4 out of 18 patients) because of good outcomes and an early response.
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan masatchmo1962@yahoo.co.jp.
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Anan
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Okuma
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ichihara
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D011446:Prospective Studies; D012008:Recurrence; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000068818:Cetuximab
keywords: K-RAS wild; S-1; cetuximab; first line chemotherapy; metastatic colorectal cancer; oxaliplatin