Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma

Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):405-9. doi: 10.1016/j.ijrobp.2006.08.076. Epub 2006 Nov 9.

Abstract

Purpose: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study.

Methods and materials: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received 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.

Results: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%.

Conclusions: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy / methods
  • Drug Administration Schedule
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy*
  • Female
  • Gene Amplification
  • Genes, erbB-2 / genetics
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Paclitaxel / administration & dosage
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Survival Analysis
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Neoplasm Proteins
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel
  • Cisplatin