First-Line Treatment for Advanced Pancreatic Cancer
Abstract
Pancreatic adenocarcinoma remains a treatment-refractory cancer. Although pancreatic adenocarcinoma is only the 10th most common cause of new cancer in the United States, it is the fourth most common cause of cancer-related death. Most cases are not suitable for resection and a majority is metastatic at presentation. Gemcitabine, with or without erlotinib, has been the standard chemotherapy in this setting but the benefit is only modest. Because gemcitabine has been considered a standard treatment for advanced pancreatic cancer for the past decade, several randomized trials have tested the combination of gemcitabine plus a second agent, including platinum based agents, topoisomerase inhibitors, taxanes, bevacizumab and cetuximab, as biologically “targeted” agents. At large this approach has not been successful and novel strategies are clearly needed. In this article, the authors summarizes the data from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, including: Abstract#175 (review of survival data in a large cohort); Abstract #286 (rapid change in prescriber patterns after the suggestion of benefit of a new regimen, FOLFIRINOX); Abstracts #238, #277, #304, and #315 (phase II trials looking at combinations that utilized EGFR blockade); Abstracts #221, #266, and #284 (phase I/II trials including VEGF blockade, anticoagulation, and traditional Chinese medicines).
Image: Columbia University College of Physicians and Surgeons. New York, NY, USA. (logo)
Downloads
References
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277-300. [PMID 20610543]
Surveillance Epidemiology and End Results (SEER). U.S. Cancer Statistics: 1999-2007 Incidence and Mortality Report. Available at http://www.seer.cancer.gov/publications/uscs.html (Accessed January 31, 2011).
Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, 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. [PMID 9196156]
Gubens MA, Kunz PL, Fisher GA, Ford JM, Lichtensztajn D, Clarke CA. Long-term survivorship in pancreatic adenocarcinoma. J Clin Oncol 2011; 29(Suppl. 4):Abstract 175.
Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 2010; 7:163-72. [PMID 20101258]
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, 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; 25:1960-6. [PMID 17452677]
Conroy T, Desseigne F, Ychou M, Ducreux M, Bouche O, Guimbaud R, et al. Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin (LV), irinotecan (I), and oxaliplatin (O)) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial. J Clin Oncol 2010; 28(15 Suppl.):Abstract 4010.
Kim GP, Foster NR, Salim M, Flynn PJ, Moore DF Jr, Zon R, et al. Randomized phase II trial of panitumumab (P), erlotinib (E), and gemcitabine (G) versus erlotinib-gemcitabine in patients with untreated, metastatic pancreatic adenocarcinoma. J Clin Oncol 2011; 29(Suppl. 4):Abstract 238.
Candamio Folgar S, Méndez Méndez C, Jorge Fernández M, Romero Reinoso C, Quintero-Aldana G, Salgado Fernández M, et al. A phase II study of capecitabine in combination with erlotinib as first-line therapy in patients with metastatic pancreatic cancer (stage IV). J Clin Oncol 2011; 29(Suppl. 4):Abstract 277.
Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27: 5513-8. [PMID 19858379]
McDermott RS, Calvert P, Parker M, Webb G, Moulton B, McCaffrey J. A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39). J Clin Oncol 2011; 29(Suppl. 4):Abstract 315.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355:2733-43. [PMID 17192538]
Munoz Llarena A, Mane J, Lopez-Vivanco G, Ruiz de Lobera A, Sancho A, Iruarrizaga E, et al. Gemcitabine (G) fixed-dose-rate infusion (FDR) plus erlotinib (E) in patients with advanced pancreatic cancer (APC). J Clin Oncol 2011; 29(Suppl. 4):Abstract 304.
Cohen DJ, Leichman LP, Love E, Ryan T, Leichman CG, Newman E, et al. Phase II study of sorafenib with gemcitabine and erlotinib (GES) in first-line advanced pancreatic cancer. J Clin Oncol 2011; 29(Suppl. 4):Abstract 266.
Khorana AA, Frine RL. Pancreatic cancer and thromboembolic disease. Lancet Oncol 2004; 5:655-63. [PMID 15522652]
Khorana AA, Ahrendt SA, Ryan CK, Francis CW, Hruban RH, Hu YC, et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007; 13:2870-5. [PMID 17504985]
Nitori N, Ino Y, Nakanishi Y, Yamada T, Honda K, Yanagihara K, et al. Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma. Clin Cancer Res 2005; 11:2531-9. [PMID 15814630]
Ramanathan RK, Gressler V, Shah S, Loury D, Hamdy A, Khorana A. Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor in patients with advanced pancreatic cancer receiving treatment with gemcitabine. J Clin Oncol 2011; 29(Suppl. 4):Abstract 221.
Meng Z, Liu L, Shen Y, Yang P, Cohen L, Huo Y, et al. A randomized phase II study of gemcitabine (G) plus the cardiac glycoside huachansu (H) in the treatment of patients with locally advanced (LAPC) or metastatic pancreatic cancer (MPC). J Clin Oncol 2011; 29(Suppl. 4):Abstract 284.
Philip PA, Benedetti J, Fenoglio-Preiser C, Zalupski M, Lenz H, O'Reilly E, et al. Phase III study of gemcitabine (G) plus cetuximab (C) versus gemcitabine in patients (pts) with locally advanced or metastatic pancreatic adenocarcinoma (PC): SWOG S0205 study. J Clin Oncol 2007; 25(18 Suppl.):Abstract LBA4509.
Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27:3778-85. [PMID 19581537]
Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28:3617-22. [PMID 20606091]
Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 2009; 27:2231-7. [PMID 19307500]
Bendell JC, Britton S, Green MR, Willey J, Lemke KE, Marshall J. Immediate impact of the FOLFIRINOX phase III data reported at the 2010 ASCO Annual Meeting on prescribing plans of American oncology physicians for patients with metastatic pancreas cancer (MPC). J Clin Oncol 2011; 29(Suppl. 4):Abstract 286.
Copyright (c) 2011 Paul E Oberstein, Muhammad Wasif Saif
This work is licensed under a Creative Commons Attribution 4.0 International License.
As a member of Publisher International Linking Association, PILA, iMedPub Group’s JOP follows the Creative Commons Attribution License and Scholars Open Access publishing policies. Journal of the Pancreas is the Council Contributor Member of Council of Science Editors (CSE) and following the CSE slogan Education, Ethics, and Evidence for Editors.