Treatment of Pancreatic Cancer
Treatment of Pancreatic Cancer
US Oncology Review 2005
Published: October 2008
Published: October 2008
Introduction
Pancreatic cancer is the fourth leading cause of cancerrelated death and has the highest case fatality rate. In 2004, approximately 31,860 new cases will be diagnosed, and 31,270 of affected patients are expected to die from their disease.1 Patients usually present with advanced disease, and two-thirds of them either have locally advanced or metastatic disease. Presentation may depend on location of the primary, with more pain in patients with tumors involving the body and tail of the pancreas, and obstructive jaundice in patients presenting with pancreatic head cancer, though symptoms including weight loss, those associated with new onset diabetes, and thrombophlebitis (Trousseau’s syndrome) can occur with either presentation. The majority of patients have ductal adenocarcinoma on pathology.
For the few selected 15% to 20% of patients who present with a resectable tumor by radiographic criteria and undergo surgery, the five-year survival rate is only 20% and it is worse in node-positive patients.2,3 Determining resectability is an important first step and in most cases can be accomplished by a computerized tomography (CT) scan optimized for pancreatic imaging. Based on CT scan findings (with help from endoscopic ultrasound if needed), patients can be categorized as those with potentially resectable cancer, borderline resectable cancer, unresectable locally advanced cancer, and metastatic pancreatic cancer. Figure 1 outlines the approach to a patient with suspected pancreatic cancer.
Resectable and Borderline Resectable Pancreatic Cancer
Staging Criteria and Role of Pancreaticoduodenectomy
American Joint Committee on Cancer (AJCC) tumor, node, metastases (TNM) staging for pancreatic cancer was revised in 2002 and is presented in Table 1.4 Based on this, stages 3 and 4 are considered unresectable. Resectability criteria include a clear fat plane around celiac and superior mesenteric arteries (SMA), a patent superior mesenteric vein (SMV) and portal vein, and no distant metastases. Patients are considered to have ‘borderline’ resectable cancer if the CT scan shows cuffing or abutment to a portion of the SMA or celiac axis, severe unilateral SMV or portal vein impingement, or gastroduodenal artery (GDA) encasement up to origin at hepatic artery. These distinctions can usually be made without a pre-operative laparoscopy or endoscopic ultrasound, although most patients, once prepared for a pancreaticoduodenectomy (Whipple procedure), do undergo intra-operative laparoscopy.An additional 20% to 40% of patients may be found to be unresectable due to a small volume of peritoneal or hepatic metastases not visualized by CT. In highvolume centers, the peri-operative mortality from pancreaticoduodenectomy is less than 2%. Even after a potentially curative resection most patients recur, and five-year survivals are rare. Important prognostic features include tumor size (<2cm), lymph node involvement, and histologic grade.2,5 Post-operative complications include anastomotic leaks, delayed gastric emptying, thrombosis, infection, and bleeding.
References:
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2. Benassai G, Mastrorilli M, Quarto G, et al., "Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas", Chir. Ital. (2000), 52: pp. 263-270.
3. Yeo C J, Cameron J L, Lillemoe K D, et al., "Pancreaticoduodenectomy for cancer of the head of the pancreas, 201 patients", Ann. Surg. (1995), 221: pp. 721-731; discussion pp. 731-733.
4. (AJCC) AJCoC:AJCC Cancer staging Manual, AJCC Cancer staging Manual (ed sixth edition), Springer-Verlag New York, Inc., 2002.
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8. Klinkenbijl J H, Jeekel J, Sahmoud T, 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: pp. 776-782; discussion pp. 782-784.
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11. Picozzi V J, Kozarek R A and Traverso L W,"Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma", Am. J. Surg. (2003), 185: pp. 476-480.
12. Spitz F R, Abbruzzese J L, Lee J E, et al., "Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas", J. Clin. Oncol. (1997), 15: pp. 928-937.
13. Moertel C G, Frytak S, Hahn R G, 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: pp. 1,705-1,710.
14. Klaassen D J, MacIntyre J M, Catton G E, et al., "Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil an Eastern Cooperative Oncology Group study", J. Clin. Oncol. (1985), 3: pp. 373-378.
15. Blackstock A W,Tepper J E, Niedwiecki D, et al., "Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas", Int. J. Gastrointest. Cancer (2003), 34: pp. 107-116.
16. Burris H A, 3rd, Moore M J,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: pp. 2,403-2,413.
17. 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: pp. 3,402-3,408.
18. A H Ko ED, B Schillinger,A P Venook, E K Bergsland, J Allen, M A Tempero; UCSF Comprehensive Cancer Center, San Francisco, CA: A phase II study of fixed-dose rate (FDR) gemcitabine plus cisplatin for metastatic pancreatic adenocarcinoma (PanCa). Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 22, No 14S (July 15 Supplement), 2004: p. 4,107, 2004.
19. Rocha Lima C M, Savarese D, Bruckner H, et al., "Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer", J. Clin. Oncol. (2002), 20: pp. 1,182-1,191.
20. Ryan D P, Kulke M H, Fuchs C S, et al.,"A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma", Cancer (2002), 94: pp. 97-103.
21. R. L. Fine DRF,W. Sherman, J. Chabot, R. Ennis, P. Xiao, S. Leventhal, S. Schreibman, J. F. Strauss, H. Richter; New York Presbyterian Hospital-Columbia University, New York, NY; Morristown Medical Oncology Associates, Morristown, NJ;Texas Oncology, Dallas,TX; Boca Raton Hospital, Boca Raton, FL:The GTX regimen: A biochemically synergistic combination for advanced pancreatic cancer (PC). Proc Am Soc Clin Oncol 22: page 281, 2003 (abstr 1129), 2003.
22. Bramhall S R, Rosemurgy A, Brown P D, et al.,"Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial", J. Clin. Oncol. (2001), 19: pp. 3,447-3,455.
23. Xiong H Q, Rosenberg A, LoBuglio A, et al.,"Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial", J. Clin. Oncol. (2004), 22: pp. 2,610-2,616.
2. Benassai G, Mastrorilli M, Quarto G, et al., "Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas", Chir. Ital. (2000), 52: pp. 263-270.
3. Yeo C J, Cameron J L, Lillemoe K D, et al., "Pancreaticoduodenectomy for cancer of the head of the pancreas, 201 patients", Ann. Surg. (1995), 221: pp. 721-731; discussion pp. 731-733.
4. (AJCC) AJCoC:AJCC Cancer staging Manual, AJCC Cancer staging Manual (ed sixth edition), Springer-Verlag New York, Inc., 2002.
5. Lim J E, Chien M W and Earle C C,"Prognostic factors following curative resection for pancreatic adenocarcinoma: a populationbased, linked database analysis of 396 patients", Ann. Surg. (2003), 237: pp. 74-85.
6. Kalser M H and Ellenberg S S,"Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection", Arch. Surg. (1985), 120: pp. 899-903.
7. Gastrointestinal Tumor Study Group, "Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer", Cancer 59: pp. 2,006-2,010, 1987.
8. Klinkenbijl J H, Jeekel J, Sahmoud T, 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: pp. 776-782; discussion pp. 782-784.
9. Neoptolemos J P, Dunn J A, Stocken D D, et al.,"Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial", Lancet (2001), 358: pp. 1,576-1,585.
10. Neoptolemos J P, Stocken D D, Friess H, et al., "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer", N. Engl. J. Med. (2004), 350: pp. 1,200-1,210.
11. Picozzi V J, Kozarek R A and Traverso L W,"Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma", Am. J. Surg. (2003), 185: pp. 476-480.
12. Spitz F R, Abbruzzese J L, Lee J E, et al., "Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas", J. Clin. Oncol. (1997), 15: pp. 928-937.
13. Moertel C G, Frytak S, Hahn R G, 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: pp. 1,705-1,710.
14. Klaassen D J, MacIntyre J M, Catton G E, et al., "Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil an Eastern Cooperative Oncology Group study", J. Clin. Oncol. (1985), 3: pp. 373-378.
15. Blackstock A W,Tepper J E, Niedwiecki D, et al., "Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas", Int. J. Gastrointest. Cancer (2003), 34: pp. 107-116.
16. Burris H A, 3rd, Moore M J,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: pp. 2,403-2,413.
17. 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: pp. 3,402-3,408.
18. A H Ko ED, B Schillinger,A P Venook, E K Bergsland, J Allen, M A Tempero; UCSF Comprehensive Cancer Center, San Francisco, CA: A phase II study of fixed-dose rate (FDR) gemcitabine plus cisplatin for metastatic pancreatic adenocarcinoma (PanCa). Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 22, No 14S (July 15 Supplement), 2004: p. 4,107, 2004.
19. Rocha Lima C M, Savarese D, Bruckner H, et al., "Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer", J. Clin. Oncol. (2002), 20: pp. 1,182-1,191.
20. Ryan D P, Kulke M H, Fuchs C S, et al.,"A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma", Cancer (2002), 94: pp. 97-103.
21. R. L. Fine DRF,W. Sherman, J. Chabot, R. Ennis, P. Xiao, S. Leventhal, S. Schreibman, J. F. Strauss, H. Richter; New York Presbyterian Hospital-Columbia University, New York, NY; Morristown Medical Oncology Associates, Morristown, NJ;Texas Oncology, Dallas,TX; Boca Raton Hospital, Boca Raton, FL:The GTX regimen: A biochemically synergistic combination for advanced pancreatic cancer (PC). Proc Am Soc Clin Oncol 22: page 281, 2003 (abstr 1129), 2003.
22. Bramhall S R, Rosemurgy A, Brown P D, et al.,"Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial", J. Clin. Oncol. (2001), 19: pp. 3,447-3,455.
23. Xiong H Q, Rosenberg A, LoBuglio A, et al.,"Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial", J. Clin. Oncol. (2004), 22: pp. 2,610-2,616.
