This Article Full Text Full Text (PDF) Erratum (v25,p2334) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dragovich, T. Articles by Abbruzzese, J. L. Search for Related Content PubMed PubMed Citation Articles by Dragovich, T. Articles by Abbruzzese, J. L. Related Articles Related Correspondence Social Bookmarking                            What's this?

Phase II Trial of Erlotinib in Gastroesophageal Junction and Gastric Adenocarcinomas: SWOG 0127

Tomislav Dragovich, Sheryl McCoy, Cecilia M. Fenoglio-Preiser, Jiang Wang, Jacqueline K. Benedetti, Amanda F. Baker, Christopher B. Hackett, Susan G. Urba, Ken S. Zaner, Charles D. Blanke, James L. Abbruzzese

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

Address reprint requests to Tomislav Dragovich, MD, PhD, Arizona Cancer Center, 1515 N Campbell Avenue, PO Box 245024, Tucson, AZ 85724; e-mail: tdragovich{at}azcc.arizona.edu

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.

Supported in part by the following Public Health Service Cooperative Agreement grants awarded by the National Cancer Institute, Department of Health and Human Services: CA38926, CA32102, CA27057, CA76448, CA13612, CA46441, CA86780, CA04919, CA42777, CA35090, CA35178, CA67663, CA35176, CA63848, CA35128, CA45808, CA45450, CA76447, CA45807, CA12644, CA58658, CA16385, CA67575, CA58686, CA45560, CA11083, CA22433, CA63850, CA58882, CA35192, CA14028, CA35431, CA58723.

Presented in part at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium, January 27-29, 2005, Hollywood, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Outcome Prediction to Erlotinib in Gastroesophageal Adenocarcinomas: Can We Improve Epidermal Growth Factor Receptor and Phospho-AKT Testing?
  Nicola Personeni
  JCO 2007 25: 910 [Full Text]

This article has been cited by other articles:

				D.G. Power and D.H. Ilson Review: Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 145 - 165. [Abstract] [PDF]

				I. Chau, A. R. Norman, D. Cunningham, J. Oates, R. Hawkins, T. Iveson, M. Nicolson, P. Harper, M. Seymour, and T. Hickish The impact of primary tumour origins in patients with advanced oesophageal, oesophago-gastric junction and gastric adenocarcinoma--individual patient data from 1775 patients in four randomised controlled trials Ann. Onc., May 1, 2009; 20(5): 885 - 891. [Abstract] [Full Text] [PDF]

				M. Hayashi, M. Inokuchi, Y. Takagi, H. Yamada, K. Kojima, J. Kumagai, T. Kawano, and K. Sugihara High Expression of HER3 Is Associated with a Decreased Survival in Gastric Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7843 - 7849. [Abstract] [Full Text] [PDF]

				N. I. Khushalani Cancer of the Esophagus and Stomach Mayo Clin. Proc., June 1, 2008; 83(6): 712 - 722. [Abstract] [Full Text] [PDF]

				W. Feng, R. E. Brown, C. D. Trung, W. Li, L. Wang, T. Khoury, S. Alrawi, J. Yao, K. Xia, and D. Tan Morphoproteomic Profile of mTOR, Ras/Raf Kinase/ERK, and NF-{kappa}B Pathways in Human Gastric Adenocarcinoma Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 195 - 209. [Abstract] [Full Text] [PDF]

				M. H. Kulke, L. S. Blaszkowsky, D. P. Ryan, J. W. Clark, J. A. Meyerhardt, A. X. Zhu, P. C. Enzinger, E. L. Kwak, A. Muzikansky, C. Lawrence, et al. Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer J. Clin. Oncol., October 20, 2007; 25(30): 4787 - 4792. [Abstract] [Full Text] [PDF]

				D. R. Ferry, M. Anderson, K. Beddard, S. Tomlinson, P. Atherfold, J. Obszynska, R. Harrison, and J. Jankowski A Phase II Study of Gefitinib Monotherapy in Advanced Esophageal Adenocarcinoma: Evidence of Gene Expression, Cellular, and Clinical Response Clin. Cancer Res., October 1, 2007; 13(19): 5869 - 5875. [Abstract] [Full Text] [PDF]

				S. Ekman, M. Bergqvist, C.-H. Heldin, and J. Lennartsson Activation of Growth Factor Receptors in Esophageal Cancer Implications for Therapy Oncologist, October 1, 2007; 12(10): 1165 - 1177. [Abstract] [Full Text] [PDF]

				M. V. Karamouzis, J. R. Grandis, and A. Argiris Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas JAMA, July 4, 2007; 298(1): 70 - 82. [Abstract] [Full Text] [PDF]

				N. Personeni Outcome Prediction to Erlotinib in Gastroesophageal Adenocarcinomas: Can We Improve Epidermal Growth Factor Receptor and Phospho-AKT Testing? J. Clin. Oncol., March 1, 2007; 25(7): 910 - 910. [Full Text] [PDF]

				T. Dragovich and C. Fenoglio-Preiser In Reply J. Clin. Oncol., March 1, 2007; 25(7): 911 - 911. [Full Text] [PDF]