This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burris, H. Articles by Rocha-Lima, C. Search for Related Content PubMed Articles by Burris, H., III Articles by Rocha-Lima, C.

Gastrointestinal Cancer

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

^aThe Sarah Cannon Research Institute, Nashville, Tennessee, USA; ^bUniversity of Miami Miller School of Medicine & Sylvester Comprehensive Cancer Center, Miami, Florida, USA

Key Words. Pancreatic cancer • Erlotinib • Cetuximab • Bevacizumab • Sorafenib • Chemotherapy

Correspondence: Howard A. Burris, III, M.D., The Sarah Cannon Research Institute, 250 25th Avenue North, Suite 110, Nashville, Tennessee 37203, USA. Telephone: 615-329-7274; Fax: 615-329-7548; e-mail: hburris{at}tnonc.com

Disclosure: H.B. has acted as a consultant to Genentech, Roche, OSI, and Lilly. C.R.-L. is on the speakers bureau for Genentech and Lilly. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article. This article discusses unlabeled, investigational, or alternative use of bevacizumab, erlotinib, and gemcitabine.

In advanced pancreatic cancer, single-agent gemcitabine became the standard therapy approximately 10 years ago. Subsequently, combinations of gemcitabine with fluorouracil, cisplatin, irinotecan, oxaliplatin, or pemetrexed produced no clear survival benefit. Among the newer approaches, targeting human epidermal growth factor receptor (HER-1/EGFR) shows promise. The U.S. Food and Drug Administration recently approved erlotinib (a HER-1/EGFR tyrosine kinase inhibitor) combined with gemcitabine for the first-line treatment of advanced pancreatic cancer. This combination showed a statistically significant survival benefit over gemcitabine alone in locally advanced or metastatic disease (the median overall survival time was 6.24 months versus 5.91 months; hazard ratio, 0.82; p = .038); however, the clinical significance of this survival difference has been questioned. Additionally, a large phase III trial where the addition of cetuximab (an anti–HER-1/EGFR monoclonal antibody [mAb]) to gemcitabine failed to result in a longer overall survival time than with gemcitabine alone has been reported. Targeting vascular endothelial growth factor (VEGF) with bevacizumab (a recombinant, humanized IgG₁ mAb that binds to VEGF) in combination with gemcitabine was investigated in a phase II trial, with promising outcomes that were unfortunately not supported by a subsequent phase III study. While the future treatment of pancreatic cancer may be influenced by the potential of certain biomarkers to predict better response to molecular-targeted therapies, allowing individualization of patient therapy, there are currently no clear candidates, and this remains an interesting area for further investigation.

This article has been cited by other articles:

				A. Y. Shaw, M. C. Henderson, G. Flynn, B. Samulitis, H. Han, S. P. Stratton, H.-H. S. Chow, L. H. Hurley, and R. T. Dorr Characterization of Novel Diaryl Oxazole-Based Compounds as Potential Agents to Treat Pancreatic Cancer J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 636 - 647. [Abstract] [Full Text] [PDF]

				U. Sahin, M. Koslowski, K. Dhaene, D. Usener, G. Brandenburg, G. Seitz, C. Huber, and O. Tureci Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development Clin. Cancer Res., December 1, 2008; 14(23): 7624 - 7634. [Abstract] [Full Text] [PDF]