title: Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus: a phase I study.
abstract: OBJECTIVE
  To conduct a phase I study incorporating trastuzumab with paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus.
  
  
  METHODS
  Patients with adenocarcinoma of the esophagus without distant organ metastases were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation 50.4 Gy. HER-2/neu-positive patients (2+/3+ by immunohistochemistry) received weekly trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg, respectively. HER-2/neu-negative patients received the same chemoradiation without trastuzumab as a control for toxicity. Dose-limiting toxicities were defined as grade 3 esophageal, cardiac, or pulmonary toxicity.
  
  
  RESULTS
  Twelve of 36 screened patients (33%) overexpressed HER-2/neu by immunohistochemistry (seven 3+ and five 2+). Eight of 12 patients with HER-2/neu overexpression by IHC had an increase in the number of HER-2/neu genes, six from amplification of the HER-2/ neu gene and two were hypderdiploid for chromosome 17. Thirty patients were enrolled (12 HER-2/neu-positive and 18 HER-2/neu-negative controls). No increase in toxicity was seen with the addition of trastuzumab. One of 12 patients in the trastuzumab arm and 8 of 17 in the control arm had grade 3 esophagitis (p < or = .026). Mean left ventricular ejection fraction for the trastuzumab group was 57% before treatment and 56% after treatment.
  
  
  CONCLUSIONS
  HER-2/neu is overexpressed in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be added at full dose to cisplatin, paclitaxel, and radiation. Future studies of trastuzumab in esophageal adenocarcinoma are indicated.
authors.affiliation: The Brown University Oncology Group, Providence, Rhode Island, USA. hsafran@lifespan.org
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.forename: Thomas
authors.initials: T
authors.lastname: DiPetrillo
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.forename: Margaret
authors.initials: M
authors.lastname: Steinhoff
authors.forename: Umadevi
authors.initials: U
authors.lastname: Tantravahi
authors.forename: Ritesh
authors.initials: R
authors.lastname: Rathore
authors.forename: Harold
authors.initials: H
authors.lastname: Wanebo
authors.forename: Marilyn
authors.initials: M
authors.lastname: Hughes
authors.forename: Chris
authors.initials: C
authors.lastname: Maia
authors.forename: James Y
authors.initials: JY
authors.lastname: Tsai
authors.forename: Terry
authors.initials: T
authors.lastname: Pasquariello
authors.forename: John R
authors.initials: JR
authors.lastname: Pepperell
authors.forename: William
authors.initials: W
authors.lastname: Cioffi
authors.forename: Teresa
authors.initials: T
authors.lastname: Kennedy
authors.forename: Laurie
authors.initials: L
authors.lastname: Reeder
authors.forename: Thomas
authors.initials: T
authors.lastname: Ng
authors.forename: Alyn
authors.initials: A
authors.lastname: Adrian
authors.forename: Lisa
authors.initials: L
authors.lastname: Goldstein
authors.forename: Bapsi
authors.initials: B
authors.lastname: Chak
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000235:genetics / Q000628:therapy*; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011878:Radiotherapy; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab; D017239:Paclitaxel; D002945:Cisplatin