Adjuvant Therapy of Pancreatic Cancer
Abstract
Strong evidence exists for the use of adjuvant chemotherapy following surgical resection in pancreatic cancer, whereas the role of adjuvant chemoradiotherapy remains controversial. The optimal time to initiate adjuvant therapy has yet to be elucidated, but is usually started 2-10 weeks following resection. First line adjuvant chemotherapy is gemcitabine, as this drug has demonstrated the better efficacy in studies. Other chemotherapeutic agents and gemcitabine in combination with biologic agents are under investigation. Furthermore, predicting response to gemcitabine based chemotherapy and other adjuvant therapies will be invaluable in guiding the practitioner to choose the most appropriate adjuvant treatment. Once adjuvant therapy has been started, accurately quantifying response to therapy is also important. The adjuvant regimen may be appropriately modified if response is inadequate. This review is an update from the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting regarding recent developments in the adjuvant treatment of pancreatic cancer with regards to choice of adjuvant regimen, timing of adjuvant therapy, predicting response to therapy and measuring response to adjuvant therapy. We will present the findings from Abstracts #4039, #4042, #e14519, #4118, and #4024. In conclusion, multiple adjuvant therapeutic regimens are associated with incremental improvements in the management of pancreatic cancer. The timing of initiation of adjuvant therapy appears to be important in outcomes. Research is ongoing into markers that can predict response to adjuvant therapy.
Image: Columbia University, New York, NY, USA (Logo)
Downloads
References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59:225-49.
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004; 363:1049-57.
Saif MW. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. JOP. J Pancreas (Online) 2007; 8:545-52.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18; 350(12):1200-10.
Oettle H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer. JAMA. 2007 Jan 17; 297:267-277.
Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8; 304(10):1073-81.
Boeck S, Ankerst DP, Heinemann V. The role of adjuvant chemotherapy for patients with resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. Oncology. 2007; 72(5-6):314-21. Epub 2008 Jan 14.
Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985; 120:899-903.
Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 1999; 230:776-82.
Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5; 299(9):1019-26. Erratum in: JAMA. 2008 Apr 23/30; 299(16):1902.
Hsu CC, Herman JM, Corsini MM, Winter JM, Callister MD, Haddock MG, et al. Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol. 2010 Apr; 17(4):981-90. Epub 2010 Jan 20.
Corsini MM, Miller RC, Haddock MG, Donohue JH, Farnell MB, Nagorney DM, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005). J Clin Oncol 2008; 26(21):3511-6.
Hazard L, Tward JD, Szabo A, Shrieve DC. Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data. Cancer. 2007 Nov 15; 110(10):2191-201.
Artinyan A, Hellan M, Mojica-Manosa P, Chen YJ, Pezner R, Ellenhorn JD, Kim J. Improved survival with adjuvant external-beam radiation therapy in lymph node-negative pancreatic cancer: a United States population-based assessment. Cancer. 2008 Jan 1; 112(1):34-42.
Stocken DD, Büchler MW, Dervenis C, Bassi C, Jeekel H, Klinkenbijl JH, et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br. J Cancer. 2005 Apr 25; 92(8):1372-81.
Butturini G, Stocken DD, Wente MN, Jeekel H, Klinkenbijl JH, Bakkevold KE, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg. 2008 Jan; 143(1):75-83; discussion 83.
Biankin AV, Kench JG, Colvin EK, Segara D, Scarlett CJ, Nguyen NQ, et al. Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer. Gastroenterology 2009; 137:558-68.
Ohuchida K, Mizumoto K, Miyasaka Y, Yu J, Cui L, Yamaguchi H, et al. Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis. J Pathol 2007; 213275-82.
Fujita H, Ohuchida K, Mizumoto K, Itaba S, Ito T, Nakata K, et al. Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. Neoplasia 2010; 12:807-17.
Drudi F, Tassinari D, Castellani C, Carloni F, Santelmo C, Tamburini E, et al. Adjuavnt treatments in pancreatic cancer: Preliminary data of a pooled analysis. J Clin Oncol 2011; 29(Suppl.):4042.
Fensterer H, Schade-Brittinger C, Mueller H, Schupfner B, Fass J, Lindig U, et al. Multicenter phase II trial to investigate safety and efficacy of an adjuvant therapy with gemcitabine and cetuximab in patients with R0 or R1 resected pancreatic cancer. J Clin Oncol 2011; 29(Suppl.):4039.
Kwon JH, Chie EK, Kim JH, Im S, Oh D, Kim Y, et al. Phase II trial of postoperative adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiation with gemcitabine in patients with resected pancreatic cancer. J Clin Oncol 2011; 29(Suppl.):4094.
Pisa A, Pericay C, Dotor E, Alfaro J, Orellana R, Pujal M, et al. The effect of time to adjuvant chemotherapy on survival in nonmetastatic resectable pancreatic adenocarcinoma: A retrospective analysis. J Clin Oncol 2011; 29(Suppl.):e14519.
Tempero MA, Winter KA, Kim GE, Kakar S, Hyun TS, Regine W, et al. S100A2 as a prognostic marker in patients receiving adjuvant therapy for pancreatic cancer (PC): A secondary analysis of RTOG 9704. J Clin Oncol 2011; 29(Suppl.):4118.
Maréchal R, Bachet J, Mackey JR, Demetter P, Graham K, Couvelard A, et al. Prediction of gemcitabine benefit after curative-intent resection of pancreatic adenocarcinoma using HENT1 and dCK protein expression. J Clin Oncol 2011; 29(Suppl.):4024.
Copyright (c) 2011 Charu Sharma, David Horowitz, John Chabot, 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.