Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus: A phase I study

Howard Safran, Thomas DiPetrillo, Ahmed Nadeem, Margaret Steinhoff, Umadevi Tantravahi, Ritesh Rathore, Harold Wanebo, Marilyn Hughes, Chris Maia, James Y. Tsai, Terry Pasquariello, John R. Pepperell, William Cioffi, Teresa Kennedy, Laurie Reeder, Thomas Ng, Alyn Adrian, Lisa Goldstein, Bapsi Chak, Hak Choy

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Purpose: To conduct a phase I study incorporating trastuzumab with paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus. Methods and Materials: 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/new-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/new-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/new-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 ≤ .026). Mean left ventricular ejection fraction for the trastuzumab group was 57% before treatment and 56% after treatment. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)670-677
Number of pages8
JournalCancer Investigation
Issue number5
StatePublished - 2004


  • Esophageal adenocarcinoma
  • HER-2/neu gene
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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