Abstract
Pancreatic cancer is a difficult and unsolved surgical problem. It remains one of the top five causes of cancer-related deaths and has the lowest 5-year survival of any cancer, largely due to late diagnosis, low resection rates, and local recurrence. Clinical trials examining the optimal timing and delivery of adjuvant therapies for pancreatic cancer have yielded controversial results. Although most experts agree that the addition of chemotherapy has survival benefit in patients with resectable pancreatic cancer, there is no consensus regarding the optimal therapeutic agents, timing (neoadjuvant versus adjuvant), and the addition of radiation therapy to the treatment regimen. Multiple phase III trials are in progress in efforts to examine these issues. Additionally, exciting progress has been made with novel chemotherapeutic combinations, and alternative treatment modalities including interferon-α, immunotherapy, and pancreatic cancer stem cells. Given the high failure pattern after surgical resection, with more than half of patients developing locoregional recurrence, all patients undergoing pancreaticoduodenectomy are candidates for adjuvant therapy.
Similar content being viewed by others
References
Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10–30.
Riela A, Zinsmeister AR, Melton LJ 3rd, Weiland LH. Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988. Mayo Clin Proc 1992;67:839–845.
Niederhuber JE, Brennen MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer 1995;76:1671–1677.
Lowenfels AB, Maisonneuve P, DiMagno EP, et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997;89:442–446.
Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993;328:1433–1437.
Ghadirian P, Boyle P, Simard A, et al. Reported family aggregation of pancreatic cancer within a population-based control study in the Francophone community in Montreal, Canada. Int J Pancreatol 1991;10:183–196.
Maringhini A, Ciambra M, Raimondo M, et al. Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer. Pancreas 1993;8:146–150.
Weirsema MJ, Norton ID, Clain JE. Role of EUS in the evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000;52:578.
Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000;52:367–371.
Tierney WM, Francis IR, Eckhauser F, et al. The accuracy of EUS and helical CT in the assessment of vascular invasion by periampullary malignancy. Gastrointest Endosc 2001;53:182–188.
Varghese JC, Farrell MA, Courtney G, et al. Role of MR cholangiopancreatograpy in patients with failed or inadequate ERCP. AJR Am J Roentgenol 1999;173:1527–1533.
Steinberg W. The clinical utility of the CA19-9 tumor-associated antigen. Am J Gastroenterol 1990;85:350–355.
Pleskow DK, Berher HJ, Gyves J, et al. Evaluation of a serological marker, CA19-9, in the diagnosis of pancreatic cancer. Ann Intern Med 1989;110:704–709.
Goggins M. Molecular markers of early pancreatic cancer. J Clin Oncol 2005;23:4524–4531.
Cao D, Hustinx SR, Sui G, et al. Identification of novel highly expressed genes in pancreatic ductal adenocarcinoma through a bioinformatics analysis of expressed sequence tags. Cancer Biol Ther 2005;3:1081–1089.
Koopman J, White CN, Zhang Z, et al. Serum markers in patients with resectable pancreatic adenocarcinoma: MIC-1 vs. CA19-9. Presented at Gastroenterology Digestive Diseases Week, Chicago, IL, May 14–19, 2005.
Koopman J, Buckhaults P, Brown DA, et al. Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res 2004;10:2386–2392.
Saldinger PF, Reilly M, Reynolds K, et al. Is CT angiography sufficient for prediction of resectability of periampullary neoplasms? J Gastrointest Surg 2000;4:233–237.
Tseng JF, Raut CP, Lee E, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004;8:935–949.
Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-FU for locally unresectable pancreatic carcinoma. Ann Surg 1979;189:205–208.
Roldan GE, Gunderson LL, Nagorney DM, et al. External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer. Cancer 1988;61:1110–1116.
Burris HA III, Moore MJ, Andersen 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;15:2403–2413.
Tempero M, Plunkett W, Ruiz Van Haperen V, et al. Randomized phase II comparison of dose-intense gemcitabine: thirty minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 2003;21:3402–3408.
Stathopoulos GP, Syrigos K, Polyzos G, et al. Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an Intergroup, multicenter, phase II study. Ann Oncol 2004;15:97–104.
Louvet C, Andre G, Lledo P, et al. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 2002;20:1512–1518.
Brembeck FH, Schoppmeyer K, Leupold U, et al. A phase II pilot trial of 13-cis retinoic acid and interferon-alpha in patients with advanced pancreatic carcinoma. Cancer 1998;83:2317–2323.
Yeo CJ, Cameron JL, Lilemoe KD, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients. Ann Surg 1995;221:721–723.
Birkmeyer JD, Warshaw AL, Finlayson SRG, et al. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery 199;126:178–183.
Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg 2003;237:74–85.
Sener SF, Fremgen A, Menck HR, et al. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg 1999;189:1–7.
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, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of the pancreas and periampullary region: phase III trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg 1999;230:776–782.
Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomized controlled trial. Lancet 2001;358:1576–1585.
Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single institution experience. Ann Surg 1997;225:621–633.
A phase III study of pre and post chemoradiation 5-FU vs pre and post chemoradiation gemcitabine for postoperative adjuvant treatment of resected pancreatic adenocarcinoma. The Radiation Therapy Oncology Group (Website). Available at: http://www.rtog.org/members/protocols/97-04/97-04.pdf. Accessed July 10, 2005.
Bakkevold KE, Arnesjo B, Dahl O, et al. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater—results of a controlled, prospective, randomized multicentre study. Eur J Cancer 1993;29A:698–703.
Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002;95:1685–1695.
Oettle H, Arning M, Langrehr J, et al. A randomized study of gemcitabine versus observation as adjuvant treatment for pancreatic cancer: results of an interim safety analysis (abstract). Proc Am Soc Clin Oncol 2001;20:46.
European Study Group for Pancreatic Cancer Trial 3. Adjuvant chemotherapies in operable pancreatic cancer. Available at: http://www.liv.ac.uk/surgery/Espac5.html. Accessed October 1, 2005.
Bosset JF, Pavy JJ, Gillet M, et al. Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer: results of a prospective study. Radiother Oncol 1992;24:191–194.
Hosotani R, Kogire M, Arii S, et al. Results of pancreatectomy with radiation therapy for pancreatic cancer. Hepatogastroenterology 1997;44:1528–1535.
Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001;8:123–132.
Mehta VK, Fisher G, Ford JA, et al. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg 2001;5:27–35.
Wolff RA, Evans DB, Crane CH, et al. Initial results of preoperative gemcitabine-based chemoradiation for resectable pancreatic adenocarcinoma. Clin Oncol 2002;21:130a.
Ammori JB, Colletti LM, Zalupski MM, et al. Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas. J Gastrointest Surg 2003;7:766–772.
Phillip PA. Gemcitabine and platinum combinations in pancreatic cancer. Cancer 2002;95:908–911.
Picozzi VJ, Kozarek RA, Traverso LW. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 2003;185:476–480.
Kaufman HL, Di Vito J, Horig H. Immunotherapy for pancreatic cancer: current concepts. Hematol Oncol Clin North Am 2002;16:159–197.
Laheru D, Jaffee EM. Pancreas cancer immunotherapy: science driving clinical progress. Nat Rev Cancer 2005;5:459–467.
Jaffee E, Hruban RH, Biedrzycki B, et al. Novel allogenic granulocyte-macrophage colony-stimulating-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001;19:145–156.
Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer: science driving clinical progress. Nat Rev Cancer 2005;5:459–467.
Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–111.
Tempero M, Behrman J, Ben-Joséf E. Pancreatic adenocarcinoma. National comprehensive cancer network. Practice Guidelines in Oncology-v.1.2005. Available at http://www.accn.org/professionals/cms/pdf/pancreatic.pdf.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Newman, E.A., Simeone, D.M. & Mulholland, M.W. Adjuvant treatment strategies for pancreatic cancer. J Gastrointest Surg 10, 916–926 (2006). https://doi.org/10.1016/j.gassur.2005.10.018
Issue Date:
DOI: https://doi.org/10.1016/j.gassur.2005.10.018