Affiliation:
1. From the University of Arizona Cancer Center, Tucson, AZ; Southwest Oncology Group Statistical Center, Seattle, WA; University of Cincinnati Medical Center, Cincinnati, OH; University of Michigan, Ann Arbor, MI; Boston University Medical Center, Boston, MA; OR Health & Science University Cancer Institute, Portland, OR; and The University of Texas M.D. Anderson Cancer Center, Houston, TX
Abstract
Purpose A phase II trial of the oral epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups: gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas. Patients and Methods Patients with a histologically proven diagnosis of adenocarcinoma of the GEJ or stomach (ST) that was unresectable or metastatic; presence of measurable disease; no prior chemotherapy for advanced or metastatic cancer; Zubrod performance status (PS) of 0 to 1; and adequate renal, hepatic, and hematologic function were treated with erlotinib 150 mg/d orally. Patient characteristics were median age, GEJ—63 years, ST—64 years; sex, GEJ—84% male and 16% female, ST—60 male and 40 female; Zubrod PS, GEJ—25 had a PS of 0 and 18 had a PS 1, ST—13 had a PS of 0 and 12 had a PS of 1. Results Percentage of common toxicities were skin rash, 86% and 72%; fatigue, 51% and 44%; and AST/ALT elevation, 28% and 28%, respectively for GEJ and ST. There has been one confirmed complete response, three confirmed partial responses (PRs) and one unconfirmed PR for an overall response probability of 9% confirmed (95% CI, 3% to 22%), all occurring in GEJ stratum. No responses were observed in ST stratum. The median survival was 6.7 months in GEJ and 3.5 months in ST stratum. Neither intratumoral EGFR, transforming growth factor–alpha or phosphorylated Akt kinase expression nor plasma proteomic analyses were predictive of clinical outcome. No somatic mutations of the EGFR exons 18, 19, or 21 were detected and there was no gross amplification of EGFR by fluorescence in situ hybridization. Conclusion Erlotinib is active in patients with GEJ adenocarcinomas, but appears inactive in gastric cancers. The molecular correlates examined were not predictive of the patient therapeutic response.
Publisher
American Society of Clinical Oncology (ASCO)
Reference26 articles.
1. Estimating the world cancer burden: Globocan 2000
2. Blot WJ, McLaughlin JK: The changing epidemiology of esophageal cancer. Semin Oncol 26:2,1999-8,
3. Dragovich T, Kindler HL: Nonsurgical palliative therapy of advanced gastric cancer, in Posner MC, Vokes EE, Weichselbaum RR, (eds): Cancer of the Upper Gastrointestinal Tract . Hamilton, Ontario, Canada, BC Decker Inc, pp 290,2002-307
4. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
5. Phase II Multi-Institutional Randomized Trial of Docetaxel Plus Cisplatin With or Without Fluorouracil in Patients With Untreated, Advanced Gastric, or Gastroesophageal Adenocarcinoma
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