This Article Full Text Full Text (PDF) 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 Philip, P. A. Articles by Erlichman, C. Search for Related Content PubMed PubMed Citation Articles by Philip, P. A. Articles by Erlichman, C. Related Articles Related Correspondence Social Bookmarking                            What's this?

Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer

Philip A. Philip, Michelle R. Mahoney, Cristine Allmer, James Thomas, Henry C. Pitot, George Kim, Ross C. Donehower, Tom Fitch, Joel Picus, Charles Erlichman

From the Karmanos Cancer Institute, Wayne State University, Detroit, MI; University of Wisconsin Comprehensive Cancer Center, Madison, WI; Howard University College of Medicine, Washington, DC; Bunting Blaustein Cancer Research Bldg, Baltimore, MD; Mayo Clinic Jacksonville, Jacksonville, FL; Mayo Clinic Scottsdale, Scottsdale, AZ; Washington University School of Medicine, St Louis, MO; and the Mayo Clinic, Rochester, MN

Address reprint requests to Philip Agop Philip, MD, PhD, Karmanos Cancer Institute, 4-HWCRC, 4100 John R St, Detroit, MI 48201; e-mail: philipp{at}karmanos.org

PURPOSE: Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months.

METHODS: Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally.

RESULTS: Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash.

CONCLUSION: Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

Supported by Grant No. NO-1 CM17104 from the National Cancer Institute.

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

• Targeting of Epidermal Growth Factor Receptor in Patients Affected by Biliary Tract Carcinoma
  Francesco Leone, Ymera Pignochino, Giuliana Cavalloni, and Massimo Aglietta
  JCO 2007 25: 1145 [Full Text]

This article has been cited by other articles:

				W. R. Jarnagin, L. H. Schwartz, D. H. Gultekin, M. Gonen, D. Haviland, J. Shia, M. D'Angelica, Y. Fong, R. DeMatteo, A. Tse, et al. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival Ann. Onc., June 2, 2009; (2009) mdp029v1. [Abstract] [Full Text] [PDF]

				B. Herberger, W. Berger, H. Puhalla, K. Schmid, S. Novak, A. Brandstetter, C. Pirker, T. Gruenberger, and M. Filipits Simultaneous blockade of the epidermal growth factor receptor/mammalian target of rapamycin pathway by epidermal growth factor receptor inhibitors and rapamycin results in reduced cell growth and survival in biliary tract cancer cells Mol. Cancer Ther., June 1, 2009; 8(6): 1547 - 1556. [Abstract] [Full Text] [PDF]

				A. Nogueira-Rodrigues, C. C. do Carmo, C. Viegas, F. Erlich, C. Camisao, K. Fontao, R. Lima, D. Herchenhorn, R. G. Martins, G. M. Moralez, et al. Phase I Trial of Erlotinib Combined with Cisplatin and Radiotherapy for Patients with Locally Advanced Cervical Squamous Cell Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6324 - 6329. [Abstract] [Full Text] [PDF]

				A. F. Hezel and A. X. Zhu Systemic Therapy for Biliary Tract Cancers Oncologist, April 1, 2008; 13(4): 415 - 423. [Abstract] [Full Text] [PDF]

				R. V. Tse, M. Hawkins, G. Lockwood, J. J. Kim, B. Cummings, J. Knox, M. Sherman, and L. A. Dawson Phase I Study of Individualized Stereotactic Body Radiotherapy for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma J. Clin. Oncol., February 1, 2008; 26(4): 657 - 664. [Abstract] [Full Text] [PDF]

				Y. J. Kim, S.-A. Im, H. G. Kim, S. Y. Oh, K. W. Lee, I. S. Choi, D. Y. Oh, S. H. Lee, J. H. Kim, D. W. Kim, et al. A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer Ann. Onc., January 1, 2008; 19(1): 99 - 103. [Abstract] [Full Text] [PDF]

				R. V. Iyer, J. Gibbs, B. Kuvshinoff, M. Fakih, J. Kepner, N. Soehnlein, D. Lawrence, and M. M. Javle A Phase II Study of Gemcitabine and Capecitabine in Advanced Cholangiocarcinoma and Carcinoma of the Gallbladder: A Single-Institution Prospective Study Ann. Surg. Oncol., November 1, 2007; 14(11): 3202 - 3209. [Abstract] [Full Text] [PDF]

				N. Yonemoto, J. Furuse, T. Okusaka, K. Yamao, A. Funakoshi, S. Ohkawa, N. Boku, K. Tanaka, M. Nagase, H. Saisho, et al. A Multi-center Retrospective Analysis of Survival Benefits of Chemotherapy for Unresectable Biliary Tract Cancer Jpn. J. Clin. Oncol., November 1, 2007; 37(11): 843 - 851. [Abstract] [Full Text] [PDF]

				I. Duran, S. J. Hotte, H. Hirte, E. X. Chen, M. MacLean, S. Turner, L. Duan, G. R. Pond, C. Lathia, S. Walsh, et al. Phase I Targeted Combination Trial of Sorafenib and Erlotinib in Patients with Advanced Solid Tumors Clin. Cancer Res., August 15, 2007; 13(16): 4849 - 4857. [Abstract] [Full Text] [PDF]

				F. Leone, Y. Pignochino, G. Cavalloni, and M. Aglietta Targeting of Epidermal Growth Factor Receptor in Patients Affected by Biliary Tract Carcinoma J. Clin. Oncol., March 20, 2007; 25(9): 1145 - 1145. [Full Text] [PDF]

				P. A. Philip, M. R. Mahoney, C. Allmer, J. Thomas, H. C. Pitot, G. Kim, R. C. Donehower, T. Fitch, J. Picus, and C. Erlichman In Reply J. Clin. Oncol., March 20, 2007; 25(9): 1145 - 1146. [Full Text] [PDF]

				A. Broniscer, J. C. Panetta, M. O'Shaughnessy, C. Fraga, F. Bai, M. J. Krasin, A. Gajjar, and C. F. Stewart Plasma and Cerebrospinal Fluid Pharmacokinetics of Erlotinib and Its Active Metabolite OSI-420 Clin. Cancer Res., March 1, 2007; 13(5): 1511 - 1515. [Abstract] [Full Text] [PDF]

				N. Steeghs, J. W. R. Nortier, and H. Gelderblom Small Molecule Tyrosine Kinase Inhibitors in the Treatment of Solid Tumors: An Update of Recent Developments Ann. Surg. Oncol., February 1, 2007; 14(2): 942 - 953. [Abstract] [Full Text] [PDF]

				M. J. Ratain and T. G. Karrison Testing the Wrong Hypothesis in Phase II Oncology Trials: There Is a Better Alternative Clin. Cancer Res., February 1, 2007; 13(3): 781 - 782. [Full Text] [PDF]

				T. J. Lansing, R. T. McConnell, D. R. Duckett, G. M. Spehar, V. B. Knick, D. F. Hassler, N. Noro, M. Furuta, K. A. Emmitte, T. M. Gilmer, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1 Mol. Cancer Ther., February 1, 2007; 6(2): 450 - 459. [Abstract] [Full Text] [PDF]