title: A Randomized Phase 2 Study of Neoadjuvant Chemoradiaton Therapy With 5-Fluorouracil/Leucovorin or Irinotecan/S-1 in Patients With Locally Advanced Rectal Cancer.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS).
  
  
  METHODS
  Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation.
  
  
  RESULTS
  One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896).
  
  
  CONCLUSIONS
  IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
authors.affiliation: Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Keum
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Hur
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byung Soh
authors.initials: BS
authors.lastname: Min
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Hyuk
authors.initials: SH
authors.lastname: Baik
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Division of Gastroenterology; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Pil
authors.initials: SP
authors.lastname: Hong
authors.affiliation: Division of Gastroenterology; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: vvswm513@yuhs.ac.
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods* / Q000401:mortality; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D010094:Oxonic Acid / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin