title: Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.
abstract: OBJECTIVE
  To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.
  
  
  METHODS
  Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.
  
  
  RESULTS
  A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.
  
  
  CONCLUSIONS
  Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Dok Hyun
authors: DH
authors: Yoon
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Seoul, Korea.
authors: Geundoo
authors: G
authors: Jang
authors: Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jong Hoon
authors: JH
authors: Kim
authors: Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Yong-Hee
authors: YH
authors: Kim
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Ji Youn
authors: JY
authors: Kim
authors: Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Hyeong Ryul
authors: HR
authors: Kim
authors: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Hwoon-Yong
authors: HY
authors: Jung
authors: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Gin-Hyug
authors: GH
authors: Lee
authors: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Ho Young
authors: HY
authors: Song
authors: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Kyung-Ja
authors: KJ
authors: Cho
authors: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jin-Sook
authors: JS
authors: Ryu
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: sbkim3@amc.seoul.kr.
authors: Sung-Bae
authors: SB
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods*; D057194:Intention to Treat Analysis; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage*; D011446:Prospective Studies; D005641:Tegafur / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid