Novel Agents and Future Prospects in the Treatment of Pancreatic Adenocarcinoma

  • Evangelos G Sarris Oncology Unit, Third Department of Medicine, University of Athens, Sotiria General Hospital. Athens, Greece
  • Kostas N Syrigos Oncology Unit, Third Department of Medicine, University of Athens, Sotiria General Hospital. Athens, Greece
  • Muhammad Wasif Saif Department of Medicine and Cancer Center, Tufts Medical Center. Boston, MA, USA
Keywords: Adenocarcinoma, Antibodies, Monoclonal, gemcitabine, Molecular Targeted Therapy, Pancreatic Neoplasms

Abstract

Pancreatic adenocarcinoma is one of the most aggressive malignancies and the fourth leading cause of cancer-related mortality in the United States. The majority of patients are diagnosed at advanced stage with inoperable locally advanced tumors or metastatic disease, and palliative chemotherapy remains the best therapeutic option for these patients. Despite intensive clinical and pre-clinical research over the last few years, the combination of the anti-metabolite drug gemcitabine with the targeted agent erlotinib, is considered standard of care in the treatment of these patients, with only minimal or modest efficacy. Therefore, novel therapeutic approaches are currently under clinical investigation in an attempt to produce more definite results for this fatal disease. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. In two studies, nimotuzumab, a monoclonal antibody against epidermal growth factor receptor (EGFR) (Abstract #4009) and bavituximab, a monoclonal antibody against phosphatidylserine (Abstract #4054) are tested in combination with gemcitabine in patients with advanced pancreatic cancer. Abstract #4012 is a study of gemcitabine with vismodegib, a novel hedgehog pathway inhibitor, whereas in Abstract #4035, toxicity and efficacy results of sunitinib in combination with gemcitabine in patients with pancreatic adenocarcinoma are presented. Lastly, safety results of pimasertib, a novel mitogen-activated protein kinase kinase (MEK) inhibitor, combined with the standard gemcitabine are presented in Abstract #4041.

Image: Sophia Engastromenou Schliemann: founder of the "Sotiria" ("Salvation") Hospital (Athens, Greece) in 1902.

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References

Hidalgo M. Pancreatic cancer. N Engl J Med. 2010; 362:1605-17.

Strimpakos A, Saif MW, Syrigos KN. Pancreatic cancer: from molecular pathogenesis to targeted therapy. Cancer Metastasis Rev 2008; 27(3):495-522.

Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15:2403-13.

Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25:1960.

Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817.

Strumberg D, Schultheis B, Ebert MP, Kerkhoff A, Hofheinz RD, et. al. Phase II, randomized, double-blind placebo-controlled trial of nimotuzumab plus gemcitabine compared with gemcitabine alone in patients (pts) with advanced pancreatic cancer (PC). J Clin Oncol 31, 2013 (suppl; abstr #4009)

Pandya SS, Wong L, Bullock AJ, Grabelsky SA, Shum MK, et. al. Randomized, open-label, phase II trial of gemcitabine with or without bavituximab in patients with nonresectable stage IV pancreatic adenocarcinoma. J Clin Oncol 31, 2013 (suppl; abstr #4054)

Faller BA, Burtness B. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy. Biologics. 2009; 3:419-28.

Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, et. al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009; 1(1):41-8.

Beck AW, Luster TA, Miller AF, Holloway SE, Conner CR, et. al. Combination of a monoclonal anti-phosphatidylserine antibody with gemcitabine strongly inhibits the growth and metastasis of orthotopic pancreatic tumors in mice. Int J Cancer. 2006; 118(10):2639-43.

Gerber DE, Stopeck AT, Wong L, Rosen LS, Thorpe PE, et. al. Phase I safety and pharmacokinetic study of bavituximab, a chimeric phosphatidylserine-targeting monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011; 17(21):6888-96.

Catenacci DVT, Bahary N, Nattam SR, Marsh RdW, Wallace JA, et. al. Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): A University of Chicago phase II consortium study. J Clin Oncol 31, 2013 (suppl; abstr #4012)

Di Marco M, Macchini M, Vecchiarelli S, Sina S, Biasco G. Hedgehog signaling: from the cuirass to the heart of pancreatic cancer. Pancreatology. 2012; 12(4):388-93.

Sandhiya S, Melvin G, Kumar SS, Dkhar SA. The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013; 4(1):4-7.

Dimou A, Syrigos K, Saif MW. Rationale for inhibition of the hedgehog pathway paracrine loop in pancreatic adenocarcinoma. JOP. 2011; 12(1):1-5.

Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med 2009; 361:2094-6.

Olson P, Hanahan D. Cancer. Breaching the cancer fortress. Science 2009; 324:1400-1.

LoRusso PM, Rudin CM, Reddy JC, Tibes R, Weiss GJ, et. al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011; 17(8):2502-11.

Verslype C, Hammel P, Hidalgo M, Macarulla T, Garcia-Carbonero R, et. al. Pimasertib plus gemcitabine in metastatic pancreatic adenocarcinoma: Results of a safety run-in part of a phase II trial. J Clin Oncol 31, 2013 (suppl; abstr #4041)

Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J Thorac Oncol. 2006; 1(1):7-9.

Richly H, Maute L, Heil G, Rüssel J, Jäger E, et. al. Prospective randomized phase II trial with gemcitabine versus gemcitabine plus sunitinib in advanced pancreatic cancer: A study of the CESAR Central European Society for Anticancer Drug Research-EWIV. J Clin Oncol 31, 2013 (suppl; abstr #4035)

Cuneo KC, Geng L, Fu A, Orton D, Hallahan DE, et. al. SU11248 (sunitinib) sensitizes pancreatic cancer to the cytotoxic effects of ionizing radiation. Int J Radiat Oncol Biol Phys 2008; 71:873–879.

Tran Cao HS, Bouvet M, Kaushal S, Keleman A, Romney E, et al. Metronomic gemcitabine in combination with sunitinib inhibits multisite metastasis and increases survival in an orthotopic model of pancreatic cancer. Mol Cancer Ther 2010; 9:2068–2078.

Awasthi N, Schwarz MA, Schwarz RE. Antitumour activity of sunitinib in combination with gemcitabine in experimental pancreatic cancer. HPB (Oxford). 2011; 13(9):597-604.

Sophia Engastromenou Schliemann: founder of the "Sotiria" ("Salvation") Hospital in 1902
Published
2013-07-10
How to Cite
Sarris, E., Syrigos, K., & Saif, M. (2013). Novel Agents and Future Prospects in the Treatment of Pancreatic Adenocarcinoma. JOP. Journal of the Pancreas, 14(4), 395-400. https://doi.org/10.6092/1590-8577/1654
Section
Highlights from the “2013 ASCO Annual Meeting”. Chicago, IL, USA. May 31 - June 4, 2013

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