title: Preoperative cetuximab, irinotecan, cisplatin, and radiation therapy for patients with locally advanced esophageal cancer.
abstract: OBJECTIVE
  To determine the efficacy and toxicity of weekly neoadjuvant cetuximab combined with irinotecan, cisplatin, and radiation therapy in patients with locally advanced esophageal or gastroesophageal junction cancer.
  
  
  METHODS
  Patients with stage IIA-IVA esophageal or gastroesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received weekly cetuximab on weeks 0-8 and irinotecan and cisplatin on weeks 1, 2, 4, and 5, with concurrent radiotherapy (50.4 Gy on weeks 1-6), followed by surgical resection.
  
  
  RESULTS
  In the first stage, 17 patients were enrolled, 16 of whom had adenocarcinoma. Because of a low pathologic complete response (pCR) rate in this cohort, the trial was discontinued for patients with adenocarcinoma but squamous cell carcinoma patients continued to be enrolled; two additional patients were enrolled before the study was closed as a result of poor accrual. Of the 19 patients enrolled, 18 patients proceeded to surgery, and 16 patients underwent an R0 resection. Three patients (16%) had a pCR. The median progression-free survival interval was 10 months, and the median overall survival duration was 31 months. Severe neutropenia occurred in 47% of patients, and severe diarrhea occurred in 47% of patients. One patient died preoperatively from sepsis, and one patient died prior to hospital discharge following surgical resection.
  
  
  CONCLUSIONS
  This schedule of cetuximab in combination with irinotecan, cisplatin, and radiation therapy was toxic and did not achieve a sufficient pCR rate in patients with localized esophageal adenocarcinoma to undergo further evaluation.
authors: Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02215, USA.
authors: Michael S
authors: MS
authors: Lee
authors: Harvey J
authors: HJ
authors: Mamon
authors: Theodore S
authors: TS
authors: Hong
authors: Noah C
authors: NC
authors: Choi
authors: Panagiotis M
authors: PM
authors: Fidias
authors: Eunice L
authors: EL
authors: Kwak
authors: Jeffrey A
authors: JA
authors: Meyerhardt
authors: David P
authors: DP
authors: Ryan
authors: Raphael
authors: R
authors: Bueno
authors: Dean M
authors: DM
authors: Donahue
authors: Michael T
authors: MT
authors: Jaklitsch
authors: Michael
authors: M
authors: Lanuti
authors: David W
authors: DW
authors: Rattner
authors: Charles S
authors: CS
authors: Fuchs
authors: Peter C
authors: PC
authors: Enzinger
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011300:Preoperative Care; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D000068818:Cetuximab; D002945:Cisplatin; D002166:Camptothecin