Treatment of Pancreatic Cancer
Treatment of Pancreatic Cancer
US Oncology Review 2005
Published: October 2008
Published: October 2008
Several cytotoxic agents have been combined with gemcitabine including cisplatin, docetaxel, irinotecan, capecitabine, and oxaliplatin.Though the response rates are slightly higher no study has shown a survival benefit (survival eight to 11 months).18-21 Studies with matrix metalloproteinase inhibitors and farnesyl transferase inhibitors have not been very promising. Currently, other targeted agents including cetuximab, erlotinib, and bevacizumab are being studied in combination with cytotoxic therapy as first-line therapy.22,23 There is no standard second-line therapy for pancreatic cancer despite the fact that several combinations have been tried with minimal benefit.
Non-chemotherapeutic Palliative Measures
Palliation of pain, biliary obstruction, and duodenal obstruction are important issues contributing to the optimal management of patients with pancreatic cancer. In a non-surgical setting, obstructive jaundice is palliated with either an expandable metal stent or a percutaneous trans-hepatic drainage. Metal stents are preferred to plastic stents because of longer functional life. There is no data suggesting a survival benefit for surgical bypass over non-surgical procedures if the patient has unresectable disease. Patients with duodenal obstruction (leading to gastric outlet obstruction) are candidates for palliative gastrojejunostomy, enteric stents or a gastrostomy–jejunostomy (G-J) drainage and feeding tube depending on the extent of disease, performance status, and life expectancy.
Prokinetic agents are sometimes helpful in cases of delayed gastric emptying. Pain control is of utmost importance because most patients with advanced disease have pain, which can have a very significant effect on their quality of life. Narcotic analgesia controls pain in most of the patients, and some patients are candidates for celiac axis neurolysis. Palliative radiation to the primary tumor is sometimes helpful for pain control, obstructive symptoms, or to control bleeding because of tumor invasion into the duodenum.
Summary
Pancreatic cancer is an aggressive disease with only 15% to 20% of patients with resectable disease surviving five years. Most patients present with either locally advanced or metastatic disease and have a poor median survival of six to 12 months. Gemcitabine is the current standard of care for advanced pancreatic cancer.
Combining other cytotoxic agents with gemcitabine has not shown a survival advantage.The role of targeted agents is under evaluation, and perhaps a better understanding of the molecular targets and pharmacogenomics in pancreatic cancer will help to develop better treatments and select responders from nonresponders thereby individualizing therapy for patients with pancreatic cancer.
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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.
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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.
