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Supportive care of the patient with locally advanced or metastatic exocrine pancreatic cancer

Carlos Fernandez-del Castillo, MD
Ramon E Jimenez, MD
Janet E Murphy, MD, MPH
Section Editors
J Thomas Lamont, MD
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Approximately 53,670 people develop cancer of the exocrine pancreas each year in the United States, and almost all are expected to die from the disease [1]. Pancreatic cancer has become the third leading cause of cancer death in the United States, with the lowest five-year survival rates of any solid tumor (8 percent) [2]. The majority of tumors (85 percent) are adenocarcinomas arising from the ductal epithelium. (See "Pathology of exocrine pancreatic neoplasms".)

Surgical resection offers the only chance of cure. However, only 15 to 20 percent of patients have resectable disease at initial diagnosis; the majority have either locally advanced or metastatic cancer. The median survival for patients with untreated, locally advanced, unresectable pancreatic cancer is 8 to 12 months and only three to six months for those with metastatic disease at presentation. For patients with locally advanced and metastatic disease, systemic chemotherapy can improve survival. In the current modern era of chemotherapy, we have achieved the best outcomes to date with the FOLFIRINOX (fluorouracil plus leucovorin, irinotecan, and oxaliplatin) regimen, demonstrating an 11.1-month median survival [3]. Survival may be longer in patients who retain a performance status that permits administration of second-line chemotherapy. At least one series reported a median survival of 18 months in fit patients receiving both the FOLFIRINOX and gemcitabine/nanoparticle albumin bound paclitaxel (nabpaclitaxel) regimens [4]. (See "Chemotherapy for advanced exocrine pancreatic cancer".)

While patients receiving chemotherapy generally report better overall quality of life, extended survival with chemotherapy does not always correspond to reduced symptom burden. Because of the anatomic location of the pancreas in the central abdomen at the root of the mesentery, most patients suffer from a significant symptom burden, and they frequently need medical attention and hospitalization for symptom management [5]. Typical patients will require numerous interventions targeting pain, anorexia and weight loss, depression and anxiety, biliary obstruction, gastric outlet obstruction, ascites, and venous thromboembolism.

This topic review will summarize an approach to these issues. A discussion on antitumor therapies for management of patients with localized pancreatic cancer (surgery, adjuvant and neoadjuvant therapy) and locally advanced pancreatic cancer (who may be eligible for chemotherapy and radiation-based therapy), and chemotherapy for advanced disease are presented separately. (See "Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis" and "Treatment for potentially resectable exocrine pancreatic cancer" and "Initial chemotherapy and radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer" and "Chemotherapy for advanced exocrine pancreatic cancer".)


All patients with newly diagnosed pancreatic cancer should have a full assessment of symptom burden, psychological status, and social supports as early as possible [6-9]. Many patients with locally advanced or metastatic disease will benefit from formal palliative care consultation and services. Early referral and initiation of palliative care services improve clinical and quality of care outcomes.

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Literature review current through: Nov 2017. | This topic last updated: Feb 27, 2017.
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  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  2. American Cancer Society. Cancer Facts and Figures 2016. Atlanta: American Cancer Society; 2016.
  3. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817.
  4. Portal A, Pernot S, Tougeron D, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer 2015; 113:989.
  5. Smyth EN, Bapat B, Ball DE, et al. Metastatic Pancreatic Adenocarcinoma Treatment Patterns, Health Care Resource Use, and Outcomes in France and the United Kingdom Between 2009 and 2012: A Retrospective Study. Clin Ther 2015; 37:1301.
  6. Khorana AA, Mangu PB, Berlin J, et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34:2541.
  7. Balaban EP, Mangu PB, Khorana AA, et al. Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34:2654.
  8. Sohal DP, Mangu PB, Khorana AA, et al. Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34:2784.
  9. Maltoni M, Scarpi E, Dall'Agata M, et al. Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial. Eur J Cancer 2016; 65:61.
  10. Jang RW, Krzyzanowska MK, Zimmermann C, et al. Palliative care and the aggressiveness of end-of-life care in patients with advanced pancreatic cancer. J Natl Cancer Inst 2015; 107.
  11. Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev 2011; :CD007519.
  12. Wong GY, Schroeder DR, Carns PE, et al. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. JAMA 2004; 291:1092.
  13. Ischia S, Ischia A, Polati E, Finco G. Three posterior percutaneous celiac plexus block techniques. A prospective, randomized study in 61 patients with pancreatic cancer pain. Anesthesiology 1992; 76:534.
  14. Rykowski JJ, Hilgier M. Efficacy of neurolytic celiac plexus block in varying locations of pancreatic cancer: influence on pain relief. Anesthesiology 2000; 92:347.
  15. Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg 1995; 80:290.
  16. Amr YM, Makharita MY. Neurolytic sympathectomy in the management of cancer pain-time effect: a prospective, randomized multicenter study. J Pain Symptom Manage 2014; 48:944.
  17. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst 1988; 80:751.
  18. Morganti AG, Trodella L, Valentini V, et al. Pain relief with short-term irradiation in locally advanced carcinoma of the pancreas. J Palliat Care 2003; 19:258.
  19. Ceha HM, van Tienhoven G, Gouma DJ, et al. Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma. Cancer 2000; 89:2222.
  20. Singh SM, Longmire WP Jr, Reber HA. Surgical palliation for pancreatic cancer. The UCLA experience. Ann Surg 1990; 212:132.
  21. Watanapa P, Williamson RC. Surgical palliation for pancreatic cancer: developments during the past two decades. Br J Surg 1992; 79:8.
  22. de Rooij PD, Rogatko A, Brennan MF. Evaluation of palliative surgical procedures in unresectable pancreatic cancer. Br J Surg 1991; 78:1053.
  23. Sohn TA, Lillemoe KD, Cameron JL, et al. Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 1999; 188:658.
  24. Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev 2006; :CD004200.
  25. Andersen JR, Sørensen SM, Kruse A, et al. Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 1989; 30:1132.
  26. Smith AC, Dowsett JF, Russell RC, et al. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet 1994; 344:1655.
  27. Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2:57.
  28. Shepherd HA, Royle G, Ross AP, et al. Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the distal common bile duct: a randomized trial. Br J Surg 1988; 75:1166.
  29. Moss AC, Morris E, Leyden J, MacMathuna P. Malignant distal biliary obstruction: a systematic review and meta-analysis of endoscopic and surgical bypass results. Cancer Treat Rev 2007; 33:213.
  30. Levy MJ, Baron TH, Gostout CJ, et al. Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: An evidence-based approach. Clin Gastroenterol Hepatol 2004; 2:273.
  31. Chen VK, Arguedas MR, Baron TH. Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: a Monte-Carlo decision analysis. Clin Gastroenterol Hepatol 2005; 3:1229.
  32. Kruse EJ. Palliation in pancreatic cancer. Surg Clin North Am 2010; 90:355.
  33. Inamdar S, Slattery E, Bhalla R, et al. Comparison of Adverse Events for Endoscopic vs Percutaneous Biliary Drainage in the Treatment of Malignant Biliary Tract Obstruction in an Inpatient National Cohort. JAMA Oncol 2016; 2:112.
  34. Nguyen-Tang T, Binmoeller KF, Sanchez-Yague A, Shah JN. Endoscopic ultrasound (EUS)-guided transhepatic anterograde self-expandable metal stent (SEMS) placement across malignant biliary obstruction. Endoscopy 2010; 42:232.
  35. Lamarca A, Rigby C, McNamara MG, et al. Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy. World J Gastroenterol 2016; 22:6065.
  36. Maire F, Hammel P, Ponsot P, et al. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas. Am J Gastroenterol 2006; 101:735.
  37. Hüser N, Michalski CW, Schuster T, et al. Systematic review and meta-analysis of prophylactic gastroenterostomy for unresectable advanced pancreatic cancer. Br J Surg 2009; 96:711.
  38. Espat NJ, Brennan MF, Conlon KC. Patients with laparoscopically staged unresectable pancreatic adenocarcinoma do not require subsequent surgical biliary or gastric bypass. J Am Coll Surg 1999; 188:649.
  39. Doberneck RC, Berndt GA. Delayed gastric emptying after palliative gastrojejunostomy for carcinoma of the pancreas. Arch Surg 1987; 122:827.
  40. Jeurnink SM, Steyerberg EW, van Hooft JE, et al. Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointest Endosc 2010; 71:490.
  41. Barkin JS, Goldberg RI, Sfakianakis GN, Levi J. Pancreatic carcinoma is associated with delayed gastric emptying. Dig Dis Sci 1986; 31:265.
  42. Kelsen DP, Portenoy RK, Thaler HT, et al. Pain and depression in patients with newly diagnosed pancreas cancer. J Clin Oncol 1995; 13:748.
  43. Cosci F, Fava GA, Sonino N. Mood and anxiety disorders as early manifestations of medical illness: a systematic review. Psychother Psychosom 2015; 84:22.
  44. Jacobsson L, Ottosson JO. Initial mental disorders in carcinoma of pancreas and stomach. Acta Psychiatr Scand Suppl 1971; 221:120.
  45. Fras I, Litin EM, Bartholomew LG. Mental symptoms as an aid in the early diagnosis of carcinoma of the pancreas. Gastroenterology 1968; 55:191.
  46. Chew HK, Wun T, Harvey D, et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166:458.
  47. Larsen AC, Dabrowski T, Frøkjær JB, et al. Prevalence of venous thromboembolism at diagnosis of upper gastrointestinal cancer. Br J Surg 2014; 101:246.
  48. Blom JW, Osanto S, Rosendaal FR. High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients. Eur J Cancer 2006; 42:410.
  49. Maraveyas A, Waters J, Roy R, et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012; 48:1283.
  50. Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer 2011; 117:1334.
  51. Blanco A, Martin A, Alfonso, P, et al. Incidence and prediction of venous thromboembolism in ambulatory patients with pancreatic cancer receiving chemotherapy (abstract 368). J Clin Oncol 2012; 30(suppl 4): abstr 368). Abstract available online at http://meetinglibrary.asco.org/content/88460-115 (Accessed on May 17, 2013).
  52. Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013; 119:648.
  53. Epstein AS, Soff GA, Capanu M, et al. Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer. Cancer 2012; 118:3053.
  54. Søgaard KK, Farkas DK, Pedersen L, Sørensen HT. Splanchnic venous thrombosis is a marker of cancer and a prognostic factor for cancer survival. Blood 2015; 126:957.
  55. Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010; 125:490.
  56. Lyman GH, Bohlke K, Khorana AA, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 2015; 33:654.
  57. Vadhan-Raj S, Zhou X, Varadhachary GR, et al. Randomized controlled trial orf dalteparin for primary thromboprophylaxis for venous thromboembolism (VTE) in patients with advanced pancreatic cancer (APC): risk factors predictive of VTE (abstract). Blood; 122 (21: 580s. Abstract availabel online at http://www.bloodjournal.org/content/122/21/580 (Accessed on February 10, 2015).
  58. Pelzer U, Opitz B, Deutschinoff G, et al. Efficacy of Prophylactic Low-Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial. J Clin Oncol 2015; 33:2028.
  59. Khorana AA, Streiff MB, Farge D, et al. Venous thromboembolism prophylaxis and treatment in cancer: a consensus statement of major guidelines panels and call to action. J Clin Oncol 2009; 27:4919.
  60. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e195S.
  61. Khorana AA, Otten HM, Zwicker JI, et al. Prevention of venous thromboembolism in cancer outpatients: guidance from the SSC of the ISTH. J Thromb Haemost 2014; 12:1928.
  62. Spyropoulos AC, Mahan C. Venous thromboembolism prophylaxis in the medical patient: controversies and perspectives. Am J Med 2009; 122:1077.
  63. Dentali F, Douketis JD, Gianni M, et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146:278.
  64. Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167:1476.
  65. Själander A, Jansson JH, Bergqvist D, et al. Efficacy and safety of anticoagulant prophylaxis to prevent venous thromboembolism in acutely ill medical inpatients: a meta-analysis. J Intern Med 2008; 263:52.
  66. Mismetti P, Laporte-Simitsidis S, Tardy B, et al. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000; 83:14.
  67. Hull RD, Schellong SM, Tapson VF, et al. Late breaking clinical trial: Extended-duration venous thromboembolism (VTE) prophylaxis in acutely ill medical patients with recent mobility: the EXCLAIM study (abstract). J Thromb Haemost 2007; 5(Suppl 1):O.
  68. Bump GM, Dandu M, Kaufman SR, et al. How complete is the evidence for thromboembolism prophylaxis in general medicine patients? A meta-analysis of randomized controlled trials. J Hosp Med 2009; 4:289.
  69. McGarry LJ, Stokes ME, Thompson D. Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients. Thromb J 2006; 4:17.
  70. Laporte S, Liotier J, Bertoletti L, et al. Individual patient data meta-analysis of enoxaparin vs. unfractionated heparin for venous thromboembolism prevention in medical patients. J Thromb Haemost 2011; 9:464.
  71. Greig MF, Rochow SB, Crilly MA, Mangoni AA. Routine pharmacological venous thromboembolism prophylaxis in frail older hospitalised patients: where is the evidence? Age Ageing 2013; 42:428.
  72. Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction). Cochrane Database Syst Rev 2014; :CD003747.
  73. Lilly CM, Liu X, Badawi O, et al. Thrombosis prophylaxis and mortality risk among critically ill adults. Chest 2014; 146:51.
  74. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 2007; 110:1723.
  75. Solari V, Jesudason EC, Turnbull JE, Yates EA. Determining the anti-coagulant-independent anti-cancer effects of heparin. Br J Cancer 2010; 103:593.
  76. Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349:146.
  77. Akl EA, Barba M, Rohilla S, et al. Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev 2008; :CD006650.
  78. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31:2189.
  79. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e419S.
  80. Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 2013; 11:56.
  81. Carrier M, Le Gal G, Cho R, et al. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost 2009; 7:760.
  82. Perez MM, Newcomer AD, Moertel CG, et al. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer 1983; 52:346.
  83. DiMagno EP, Malagelada JR, Go VL. The relationships between pancreatic ductal obstruction and pancreatic secretion in man. Mayo Clin Proc 1979; 54:157.
  84. Matsumoto J, Traverso LW. Exocrine function following the whipple operation as assessed by stool elastase. J Gastrointest Surg 2006; 10:1225.
  85. Kato H, Nakao A, Kishimoto W, et al. 13C-labeled trioctanoin breath test for exocrine pancreatic function test in patients after pancreatoduodenectomy. Am J Gastroenterol 1993; 88:64.
  86. Sabater L, Ausania F, Bakker OJ, et al. Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery. Ann Surg 2016; 264:949.
  87. Saito T, Hirano K, Isayama H, et al. The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study. Pancreas 2017; 46:341.
  88. Pancreatric Section, British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, et al. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut 2005; 54 Suppl 5:v1.
  89. Landers A, Muircroft W, Brown H. Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer. BMJ Support Palliat Care 2016; 6:75.
  90. Whitcomb DC, Lehman GA, Vasileva G, et al. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol 2010; 105:2276.
  91. Bruno MJ, Haverkort EB, Tijssen GP, et al. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998; 42:92.
  92. Braga M, Cristallo M, De Franchis R, et al. Pancreatic enzyme replacement therapy in post-pancreatectomy patients. Int J Pancreatol 1989; 5 Suppl:37.
  93. Guarner L, Rodríguez R, Guarner F, Malagelada JR. Fate of oral enzymes in pancreatic insufficiency. Gut 1993; 34:708.
  94. Domínguez-Muñoz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol 2011; 26 Suppl 2:12.
  95. Domínguez-Muñoz JE, Iglesias-García J, Iglesias-Rey M, Vilariño-Insua M. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut 2006; 55:1056.
  96. Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, Iglesias-Rey M. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2007; 5:484.
  97. Holtmann G, Kelly DG, Sternby B, DiMagno EP. Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes. Am J Physiol 1997; 273:G553.
  98. Suzuki A, Mizumoto A, Rerknimitr R, et al. Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs. Gastroenterology 1999; 116:431.
  99. Hicks AM, Chou J, Capanu M, et al. Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications. Clin Colorectal Cancer 2016; 15:360.