Chemoradiotherapy in pancreatic carcinoma

Sushmita Pathy; Subhash Chander

doi:10.4103/0971-5851.60049

Indian Journal of Medical and Paediatric Oncology, Table of Contents

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2009; 30(02): 55-60
DOI: 10.4103/0971-5851.60049

REVIEW ARTICLE

Chemoradiotherapy in pancreatic carcinoma

Authors

Sushmita Pathy

Department of Radiation Oncology, All India Institute Of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
Subhash Chander

Department of Radiation Oncology, All India Institute Of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India

Abstract

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Abstract

Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

Keywords

Carcinoma - chemoradiation - pancreas

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References

References
1 American Cancer Society.: Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society, 2006.
2 National Cancer Registry Program. Biennial report. Population based cancer registries 1988-89. An epidemiological study. Cancer Incidence 1992. p. 10-4.
3 Allema JH, Reinders ME, van Gulik TM, Koelemay MJ, van Leeuwen DJ, de Wit LT, et al. Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region. Cancer 1995;75:2069.
4 Lowy AM, Leach SD. Adjuvant/neoadjuvant chemoradiation for gastric and pancreatric cancer. Oncology 1999;5:121.
5 Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy: 118 consecutive resections without an operative mortality. Ann Surg 1990;211:447.
6 Kleeff J, Michalski C, Friess H, Buchler MW. Pancreatic cancer: from bench to 5-year survival. Pancreas 2006:33:111.
7 Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma: Clinicopathologic analysis of 5-year survivors. Ann Surg 1996;223:273.
8 Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma (discussion). Am J Surg 1993;16:72.
9 Kalser MH, Ellenberg SS. Pancreatic cancer: Adjuvant combined radiation and chemotherapy following curative resection. GITSG. Arch Surg 1985;120:899.
10 Foo ML, Gunderson LL, Nagorney DM, McLlrath DC, van Heerden JA, Robinow JS, et al. Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation + 5 FU. Int J Pediatr Oncol Biol Phys 1993;26:483-9.
11 Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticochodenectomy resection for pancreatic adenocarcinoma: Postoperative adjuvant themoirradiation improves survival. A prospective single institute experience. Ann Surg 1997;225:621-33.
12 Whittington R, Bryer MP, Haller DG, Solin LJ, Rosato EF. Adjuvant therapy of resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1991;21:1137-43.
13 Bosset JF, Pavy JJ, Gillet M, Mantion G, Pelissier E, Schraub S. Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer. Results of a prospective study. Radiother Oncol 1992;24:191-4.
14 Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, et al. Pancreaticoduodenectomy for cancer of the head of thepancreas. 201 patients. Ann Surg. 1995 Jun;221(6):721-31; discussion 731-3. PubMed PMID: 7794076; PubMed Central PMCID: PMC1234702.
15 Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, et al. Adjuvant radiotherapy and 5 FU after curative resection of cancer of the pancreas and periampullary region. Ann Surg 1999;230:776-82.
16 Neopltolemos JP, Dunn JA, Moffitt DD. ESPAC-1 interim results. A European, randomized study to assess the role of adjuvant chemotherapy (5 FU + Folinic Acid) and adjuvant chemoradiation (40 Gy + 5 FU) in resectable pancreatic cancer. Proc Am Soc Clin Oncol 2000;19:238a.
17 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;350:1200-10.
18 Johnstone PA, Sindelar NF. Patterns of disease recurrence following definitive therapy and adenocarcinoma of the pancreas using surgery and adjuvant radiotherapy: correlation of clinical trial. Int J Radiat Oncol Biol Phys 1993;27:831-4.
19 Fossati V, Cattaneo GM, Zerbi A, Galli L, Bordogna G, Reni M, et al. The role of IORT by electron beam and combination of adjuvant chemotherapy and external radiotherapy in carcinoma of pancreas. Thorax 1995;81:23-31.
20 Zerbi A, Fossati V, Parolini D, Carlucci M, Balzano G, Bordogna G, et al. Intraoperative radiation therapy adjuvant to resection in treatment of pancreatic cancer. Cancer 1994;73:2930-5.
21 Gunderson LL, Haddock MG, Burch P, Nagorney D, Foo ML, Todoroki T. Future role of radiotherapy as a component of treatment in biliopancreatic cancers. Ann Oncol 1999;10:291-5.
22 Sindelar WF, Kinsella TJ. Studies of intraoperative radiotherapy in carcinoma of the pancreas. Ann Oncol 1999;10:226-30.
23 Yamaguchi K, Nakamura K, Kobayashi K, Nakano K, Konomi H, Mizumoto K, et al. ERT following IORT improves survival of patients with resectable pancreatic cancer Hepatogastroenterology 2005;52:1244-9.
24 Tsujie M, Nakamori S, Tanaka E, Nagano H, Umeshita K, Dono K, et al. Phase I/II trial of hyperfractionated accelerated chemoradiotherapy for unresectable advanced pancreatic cancer. Jpn J Clin Oncol 2006;36:504-10.
25 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;15:2043-13.
26 Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd. Phase III study of gemcitabnine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2292. J Clin Oncol 2002;20:3270-5.
27 Rocha Lima CM, Green MR, Rotche R, Miller WH Jr, Jeffrey GM, Cisar LA, et al. Iritnotecan asnd gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patient with locally advanced or metastatic pancreatic cancer despitre increased tumor response rates. J Clin Oncol 2004;22:3776-83.
28 Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 2006;24:3946-52.
29 Hoffman JP, McGlinn CJ, Szarka C. A phase I study of preoperative gemcitabine with radiation therapy followed by postoperative gemcitabine for patients with localized resectable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1998;17:283.
30 Hoffman JP, Weese JL, Solin LJ, Engstrom P, Agarwal P, Barber LW, et al. A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas. Am J Surg 1995;169:71-7.
31 Pendurthi TK, Hoffman JP, Ross E, Johnson DE, Eisenberg BL. Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma. Am Surg 1998;64:686-92.
32 Massucco P, Capussotti L, Magnino A, Sperti E, Gatti M, Muratore A, et al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: Analysis of perioperative outcome and survival. Ann Surg Oncol 2006; 13:1201-8.
33 Komaki R, Hansen R, Cox JD, Wilson JF. Phase I, II study of prophylactic hepatic irradiation with local irradiation and systemic chemotherapy for adenocarcinoma and pancreas. Int J Radiat Oncol Biol Physcs 1988;15:1447-52.
34 Evans DB, Abbruzzese JL, Cleary KR, Buchholz DJ, Fenoglio CJ, Collier C, et al. Preoperative chemoradiation for adenocarcinoma of the pancreas: Excessive toxicity of prophylactic hepatic irradiation. Int J Radiat Oncol Biol Phys 1995;33:913-8.
35 Warshaw AL, Fernández-del Castillo C. Pancreatic carcinoma. N Engl J Med 1992;326:455-65.
36 O′Connor JK, Sause WT, Hazard LJ, Belnap LP, Noyes RD. Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma. Int J Radiat Oncol Biol Phys 2005;63:1060-6.
37 Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA. Combined 5 FU and supervoltage RT for locally unresectable GI cancer. Lancet 1969;2:865-7.
38 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 1987;189:205-8.
39 Moertel CG, Frytak S, Hahn RG, O′Connell MJ, Reitemeier RJ, Rubin J, et al. Therapy of locally unresectable pancreatic carcinoma. A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5 FU) and high dose radiation + 5 FU cancer 1981;48:1705-10.
40 Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG. Treatment of locally unresectable cancer of stomach and pancreas: A randomized comparison of 5 FU alone with radiation plus concurrent maintenance 5 FU. An ECOG study. J Clin Oncol 1985;3:373-8.
41 Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of pancreas: Comparison of combined modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988;80:751-5.
42 Seydel HG, Stablein DM, Leichman LP, Kinzie JJ, Thomas PR. Hyperfractionated radiation and chemotherapy for unresectable localized adenocarcinoma of the pancreas. The Gastrointestinal Tumor Study Group experience. Cancer 1990;65:1478-82.
43 Abe M, Shibamoto Y, Ono K, Takahashi M. Intraoperative radiation therapy for carcinoma of the stomach of pancreas. Front Radiat Ther Oncol 1991;25:258-69.
44 Ma JH, Patrut E, Schmidt J, Knaebel HP, Buchler MW, Marten A. Synergistic effects of interferon-a in combination with chemoradiation on human pancreatic adenocarcinoma. World J Gastroenterol 2005;11:1521-8.
45 Abou-Alfa GK, Letourneau R, Harker G, Modiano M, Hurwitz H, Tchekmedyian NS, et al. Randomized phase iii study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol 2006;24:4441-7.
46 Touroutoglou N, Padzur R. Thymidylate synthase inhibitors. Clin Cancer Res 1996;2:227-43.