Adjuvant Therapy for Pancreatic Cancer
Survival for patients with pancreas cancer is correlated to stage. Only 20% of patients present with localized disease amenable to potentially curative resection but, despite resection, the 5-year survival rate for early stage patients remains less than 25%. Current accepted standard of care is adjuvant gemcitabine following curative resection but there have been no conclusions regarding the role or timing of adjuvant chemoradiation. Although systemic disease represents the major risk for failure following resection, there are patients who would benefit from adjuvant local therapy that remain difficult to identify at present. This year at 2014 ASCO Gastrointestinal Cancers Symposium, Cho at al. (Abstract #325) presented the results of adjuvant gemcitabine with the addition of docetaxel followed by 5-FU chemoradiation for patients with resected pancreatic cancer. Kumar et al. (Abstract #330) compared adjuvant chemoradiation to adjuvant chemotherapy. Lastly Heestand et al. (Abstract #176) used a novel way to look at different biomarkers in serum of patients in the RTOG 9407 study and evaluated the survival depending on the type of chemotherapy used. A lower serum CEA and CA 19-9 gave a better overall survival in all patients which has already been established. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an overall survival benefit from adjuvant gemcitabine, but not from 5-FU.
Image: Schema of the treatment with gemcitabine plus docetaxel (Figure 1)
American Cancer Society. Cancer Facts & Figures 2013. Atlanta, Ga: American Cancer Society; 2013.
Saif MW. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. JOP. J Pancreas (Online) 2007; 8:545-52.
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.
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.
Uesaka K, Fukutomi A, Boku N, Kanemoto H et al. Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). J Clin Oncol 30: 2012 (suppl 34; abstr 145).
Cho M, Wang-Gillam A, Gao F, Linehan D, Hawkins WG, Suresh R, Fournier C, Picus J, Tan B. Adjuvant gemcitabine plus docetaxel followed by 5FU chemoradiation for patients with resected pancreaticobiliary cancers: A single institution phase II study. 2014 Gastrointestinal Cancers Symposium J Clin Oncol 32, 2014 (suppl 3; abstr 325)
Kumar A, Falk G, Stephans KL, Walsh M, Pelley RJ, Abdel-Wahab M; Adjuvant chemoradiation to improve survival compared to adjuvant chemotherapy in selected patients with pancreatic cancer. 2014 Gastrointestinal Cancers Symposium J Clin Oncol 32, 2014 (suppl 3; abstr 330)
Heestand GH, Murphy JD, Moughan J, Regine W, Luo J, Graber MS, Kunz PL, Fisher GA, Guha C, Lin B, Mowat RB, Gaur R, Buyyounouski MK, Chen Y, Chang DT, Koong A. A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704. J Clin Oncol 32, 2014 (suppl 3; abstr 176)
Liao W, Chien KL, Lin YL, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. The Lancet Oncology, Volume 14, Issue 11, Pages 1095 - 1103, October 2013
Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood). 2006 Jan;231(1):20-7.
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