Pilot study of gefitinib, oxaliplatin, and radiotherapy for esophageal adenocarcinoma tissue effect predicts clinical response

Milind Javle, Amitkumar Pande, Renuka Iyer, Gary Yang, Charles LeVea, Gregory Wilding, Jennifer Black, Hector Nava, Chukwumere Nwogu

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Purpose: Overexpression of epidermal growth factor receptor (EGFR) in esophageal cancer is associated with poor prognosis. Preclinical studies indicate synergism between the EGFR inhibitor gefitinib and oxaliplatin or radiotherapy (RT). We report here early results of a planned phase I/II study of gefitinib, oxaliplatin, and RT for locally advanced, unresectable esophageal cancer. Methods and Materials: The protocol consisted of oral gefitinib 250 mg daily for 1 year plus intravenous oxaliplatin 85 or 100 mg/m2 on days 1, 15, and 29, and RT (50.4 Gy in 28 1.8-Gy fractions). Four-quadrant biopsies were obtained at 1-cm intervals along the length of the tumor before and after treatment and the specimens were immunostained for EGFR, Erk, Akt, and their phosphorylated (activated) forms. Results: Enrollment was halted at 6 evaluable cases [all male; median age, 72.5 years (range, 51-75); and all with Eastern Cooperative Oncology Group performance status of 1]. All 6 tumors were adenocarcinomas; 5 were stage III and 1 stage IVA. Oxaliplatin was given at 85 mg/m2 in 3 cases and at 100 mg/m2 in 3 cases. Gefitinib therapy lasted a median 24 weeks; the median number of oxaliplatin doses was 6.5. Best responses were mucosal complete response (n=1), partial response (n = 1), stable disease (n = 1), and progressive disease (n = 3). EGFR was expressed by tumor in 5 cases and Erk and Akt in 6 cases before treatment; no changes were noted after treatment. EGFR expression did not correlate with survival or response. No grade 4 toxicities were noted; grade 3 toxicities were diarrhea (n = 1), vomiting (n = 1), fatigue (n = 1), and constipation (n = 2). Median overall and disease-free survival times were 10.8 months and 8.4 months. Conclusions: Gefitinib in combination with oxaliplatin and RT was tolerable, but had limited clinical activity and did not down-regulate total or activated EGFR, Akt, or Erk in esophageal tumor samples.

Original languageEnglish (US)
Pages (from-to)329-334
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume31
Issue number4
DOIs
StatePublished - Aug 2008

Keywords

  • Chemoradiation
  • EGFR
  • Esophageal cancer
  • Gefitinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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