Abstract
In western countries, carcinoma of the pancreas remains the most lethal of the common malignancies. Even the favorable “organ-confined” tumors present a considerable challenge. The lack of anatomic barriers to local infiltration and the biological propensity for early lymphatic, perineural, and vascular invasion are nearly insurmountable obstacles to complete surgical eradication of this malignancy. Various combinations of chemotherapy and radiotherapy (RT) have been used with marginal but measurable success. Earlier trials conducted by the Gastrointestinal Tumor Study Group established roles for 5-fluorouracil chemotherapy and RT in the treatment of patients with resectable or locally advanced pancreatic cancer. More recently, computed tomography-guided conformal RT and a variety of intraoperative RT techniques have enabled more reliable sterilization of the local surgical field and escalation of doses to potentially curative levels (7000 cGy) for unresectable lesions. Chemotherapy dose intensification through the use of portable programmable pumps for protracted venous infusions and the development of active systemic agents in addition to 5-fluorouracil suggest that an effective combination chemotherapeutic regimen might soon be developed. This report reviews the current standards of practice and integrates recent developments to construct a modern algorithm for the use of chemoradiotherapy in the management of localized (nonmetastatic) pancreatic cancer. The likely directions of future investigations are also discussed.
Similar content being viewed by others
REFERENCES
Douglass HO Jr. Adjuvant therapy for pancreatic cancer. World J Surg 1995;19:270–4.
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;225:621–33.
Poen JC, Collins HL, Niederhuber JE, et al. Chemo-radiotherapy for localized pancreatic cancer: increased dose intensity and reduced acute toxicity with concomitant radiotherapy and protracted venous infusion of 5-fluorouracil. Int J Radiat Oncol Biol Phys 1998;40:93–9.
Burris HA III, 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.
Allema JH, Reinders ME, van Gulik TM, et al. Portal vein resection in patients undergoing pancreaticoduodenectomy for carcinoma of the pancreatic head. Br J Surg 1994;81:1642–6.
Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 1997;15:928–37.
Coia L, Hoffman J, Scher R, et al. Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum. Int J Radiat Oncol Biol Phys 1994;30:161–7.
Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB III. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: An Eastern Cooperative Oncology Group Study. J Clin Oncol 1998;16:317–23.
Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: the Gastrointestinal Tumor Study Group. Cancer 1981;48:1705–10.
Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combinedmodality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988;80:751–5.
Dobelbower RR Jr, Merrick HW III, Ahuja RK, Skeel RT. 125I Interstitial implant, precision high-dose external beam therapy and 5-FU for unresectable adenocarcinoma of pancreas and extrahepatic biliary tree. Cancer 1986;58:2185–95.
Mohiuddin M, Rosato F, Barbot D, Schuricht A, Biermann W, Cantor R. Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1992;23:305–11.
Roldan GE, Gunderson LL, Nagorney DM, et al. External beam versus intraoperative and external beam irradiation of locally advanced pancreatic cancer. Cancer 1988;61:1110–6.
Mohiuddin M, Regine WF, Stevens J, et al. Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. J Clin Oncol 1995;13:2764–8.
Rougier P, De Forni M, Adenis A, et al. Phase II study of Taxotere (RP56976) in pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1994;13:200.
Hennequin C, Giocanti N, Favaudon V. Interaction of ionizing radiation with paclitaxel (Taxol) and docetaxel (Taxotere) in HeLa and SQ20B cells. Cancer Res 1996;56:1842–50.
Safran H, King T, Choy H, et al. Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study. J Clin Oncol 1997;15:901–7.
Abbruzzese JL, Levin B, Ajani JA, et al. A phase I trial of recombinant human interferon-gamma and recombinant human tumor necrosis factor in patients with gastrointestinal cancer. Cancer Res 1989;49:4057–61.
Gibbs JB, Oliff A, Kohl NE. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 1994;77:175–8.
Gjertsen MK, Bakka A, Frievik J, et al. Ex vivo Ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Int J Cancer 1996;65:450–3.
Rasmussen HS, McCann PP. Matrix metalloproteinase inhibition as a novel anticancer strategy. Pharmacol Ther 1997;75:69–75.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poen, J.C., Ford, J.M. & Niederhuber, J.E. Chemoradiotherapy in the Management of Localized Tumors of the Pancreas. Ann Surg Oncol 6, 117–122 (1999). https://doi.org/10.1007/s10434-999-0117-1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10434-999-0117-1