title: A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer (SHOGUN trial).
abstract: BACKGROUND
  The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.
  
  
  METHODS
  Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained.
  
  
  RESULTS
  Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses.
  
  
  CONCLUSIONS
  The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.
  
  
  BACKGROUND
  This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).
authors.affiliation: Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. sochan31@hotmail.com.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ishihara
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. satoshi.matsusaka@jfcr.or.jp.
authors.forename: Satoshi
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authors.lastname: Matsusaka
authors.affiliation: Department of General & Gastroenterological Surgery, Osaka Medical College, 2-7, Daigaku-cho, Takatsuki, Osaka, 569-8686, Japan. sur086@poh.osaka-med.ac.jp.
authors.forename: Keisaku
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Surgery, School of Medicine Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. hisahorie@jichi.ac.jp.
authors.forename: Hisanaga
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authors.lastname: Horie
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University, 65, Tsurumai-cho, Syowa-ku, Nagoya, Aichi, 466-8550, Japan. kuehara@med.nagoya-u.ac.jp.
authors.forename: Keisuke
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authors.affiliation: Department of Radiation Oncology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. oguchi@jfcr.or.jp.
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authors.affiliation: Department of Radiation Oncology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. keiko.nemoto@jfcr.or.jp.
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authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. mueno@jfcr.or.jp.
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authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. mizunuma@jfcr.or.jp.
authors.forename: Nobuyuki
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authors.affiliation: Department of Radiology, Osaka Medical College, 2-7, Daigaku-cho, Takatsuki, Osaka, 569-8686, Japan. taijushimbo@hotmail.com.
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authors.affiliation: Department of Radiology, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. dka-tky@umin.ac.jp.
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authors.affiliation: Department of General & Gastroenterological Surgery, Osaka Medical College, 2-7, Daigaku-cho, Takatsuki, Osaka, 569-8686, Japan. sur017@poh.osaka-med.ac.jp.
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authors.affiliation: Department of Surgery, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. yhashi@med.teikyo-u.ac.jp.
authors.forename: Yojiro
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authors.affiliation: Department of Radiology, School of Medicine Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. mnakazaw@jichi.ac.jp.
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authors.affiliation: Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. sunami-1su@h.u-tokyo.ac.jp.
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authors.affiliation: Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. kz-kawai@mvd.biglobe.ne.jp.
authors.forename: Kazushige
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authors.affiliation: Department of Radiology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yamachan07291973@yahoo.co.jp.
authors.forename: Hideomi
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authors.lastname: Yamashita
authors.affiliation: Department of Radiology, Nagoya University, 65, Tsurumai-cho, Syowa-ku, Nagoya, Aichi, 466-8560, Japan. tohruokada@med.nagoya-u.ac.jp.
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authors.affiliation: Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. ishikawa@jfcr.or.jp.
authors.forename: Yuichi
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authors.lastname: Ishikawa
authors.affiliation: Japan Clinical Cancer Research Organization, 7F Ginza Wing Bldg. 1-14-5, Ginza, Chuo-ku, Tokyo, 104-0061, Japan. nakajima@jfcr.or.jp.
authors.forename: Toshifusa
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mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D010388:Pelvis / Q000528:radiation effects*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D005641:Tegafur / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid