title: Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).
abstract: BACKGROUND
  Preoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary end point of a pathologic complete response (pCR) ≥35%.
  
  
  METHODS
  From 15 January 2009 to 22 July 2011, 70 patients with locally advanced but resectable distal esophageal adenocarcinoma were enrolled. Patients received docetaxel (40 mg/m(2)), cisplatin (40 mg/m(2)), and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with RT (5040 cGy, 180 cGy/day × 28 days) beginning week 5. Resection was planned after completing CRT. PCR was defined as no viable residual tumor cells. Secondary objectives included near-pCR (≤10% viable cancer cells), toxicity, and overall and disease-free survival. Adverse events were graded using the CTCAE Version 3.0.
  
  
  RESULTS
  Five of 70 patients were ineligible. Of 65 eligible patients (59 M; median age 61), 11 did not undergo surgery, leaving 54 assessable. PCR rate was 33.3% and near-pCR was 20.4%. Secenty-three percent of patients completed DCP (n = 70) and 92% completed RT. 48.5% had toxicity ≥grade 4. Lymphopenia (43%) was most common. Operative mortality was 3.7%. Adult respiratory distress syndrome was encountered in two patients (3.7%). At median follow-up of 26.3 months, median overall survival was 19.4 months and 3-year overall survival was 38.6% (95% confidence interval 24.5% to 60.8%).
  
  
  CONCLUSIONS
  Neoadjuvant CRT with DCP is active (pCR + near-pCR = 53.7%) but toxicity is significant. Further evaluation of this regimen in an unselected population is not recommended.
  
  
  BACKGROUND
  NCT00757172.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis.
authors.forename: A C
authors.initials: AC
authors.lastname: Lockhart
authors.forename: C E
authors.initials: CE
authors.lastname: Reed
authors.forename: P A
authors.initials: PA
authors.lastname: Decker
authors.forename: B F
authors.initials: BF
authors.lastname: Meyers
authors.forename: M K
authors.initials: MK
authors.lastname: Ferguson
authors.forename: A R
authors.initials: AR
authors.lastname: Oeltjen
authors.forename: J B
authors.initials: JB
authors.lastname: Putnam
authors.forename: S D
authors.initials: SD
authors.lastname: Cassivi
authors.forename: A J
authors.initials: AJ
authors.lastname: Montero
authors.forename: T E
authors.initials: TE
authors.lastname: Schefter
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000401:mortality / Q000628:therapy*; D004943:Esophagogastric Junction / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D000077544:Panitumumab; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D043823:Taxoids; D000077143:Docetaxel; D000077544:Panitumumab; D002945:Cisplatin
keywords: chemotherapy; epidermal growth factor receptor; esophageal cancer; esophagectomy; neoadjuvant therapy; radiation therapy