PERT for Treatment of Exocrine Pancreatic Insufficiency in Patients With Unresectable Pancreatic Cancer

PERT for Treatment of Exocrine Pancreatic Insufficiency in Patients With Unresectable Pancreatic Cancer

Pancreatic Enzyme Replacement Therapy (PERT) for Treatment of Exocrine Pancreatic Insufficiency in Patients With Unresectable Pancreatic Cancer

Does pancreas enzyme replacement (PERT) decrease weight loss and improve quality of life in patients with unresectable pancreatic cancer?

Randomized, double-blind clinical trial aiming to assess the impact of pancreas enzyme replacement therapy in weight loss and quality of life. Prevalence of pancreatic exocrine insufficiency (PEI) will be determined with fecal elastase-1 test (FE1) in patients with unresectable pancreatic cancer, without evidence of pancreatic duct (PD) or common bile duct (CBD) obstruction based on MRI or / and endoscopic ultrasound (EUS). Patients with PEI (FE1 <200) receive Pertzye or placebo in a cross-over fashion, each for 4 weeks. Body weight, body mass index (BMI), body composition (Bioimpedance), are measured at the time of diagnosis of PEI and at 4 and 10 weeks of cross-over treatment. Baseline measurement of Vitamin D-25, Vitamin A, iron (ferritin, total iron binding capacity (TIBC), iron), Vitamin B12,Tissue transglutaminase IgA (tTG) with total Immunoglobulin A (IgA). Quality of Life (pain, diarrhea, weight, bloating, etc.) assessed at 0,4,10 weeks with the Functional Assessment of Cancer Therapy for patients with liver, bile duct and pancreas cancer (FACT-Hep) for physical, social, emotional, and functional quality of life.

Placebo oral capsule: 3 capsules taken with or after meals, and 2 capsules taken with or after snacks during 4 weeks in first intervention period, and Pancrelipase 3 capsules are taken with or after meals (4800 lipase units) and 2 capsules with or after snacks (3200 lipase units) during 4 weeks in second intervention period (after 2 week washout period).

Pancrelipase 3 capsules are taken with or after meals (4800 lipase units) and 2 capsules with or after snacks (3200 lipase units) during 4 weeks in first intervention period, and Placebo oral capsule: 3 capsules taken with or after meals, and 2 capsules taken with or after snacks during 4 weeks in second intervention period (after 2 week washout period).

Lipase 16,000 United States Pharmacopoeia (USP) units, protease 57,500 USP units, and amylase 60,500 USP units

Quality of life will be measured using the FACT-Hep questionnaire (Functional Assessment of Cancer Therapy for patients with liver, bile duct and pancreas cancer) for physical, social, emotional, and functional quality of life at the time of accrual, and at 4 weeks of cross-over treatment. The FACT-Hep scale consists of 45 questions, with possible responses ranging from 0 (not at all) to 4 (very much). Therefore, the total score can range from 0 (not at all - no issues) to 180 (very much - very poor quality of life).

Quality of life will be measured using the FACT-Hep questionnaire (Functional Assessment of Cancer Therapy for patients with liver, bile duct and pancreas cancer) for physical, social, emotional, and functional quality of life at the time of accrual, and at 10 weeks of cross-over treatment. The FACT-Hep scale consists of 45 questions, with possible responses ranging from 0 (not at all) to 4 (very much). Therefore, the total score can range from 0 (not at all - no issues) to 180 (very much - very poor quality of life).

Body weight composition will be determined at the time of accrual, and at 4 and 10 weeks of cross-over treatment.

Inclusion Criteria: Patients 18-80 years Underlying pancreatic adenocarcinoma, unresectable (local invasion or distant metastasis) On established chemotherapy regimen for pancreas cancer, which will be continued over the time of study Fecal elastase-1 test (FE1) less than 200 mcg pancreatic elastase/g stool Exclusion Criteria: Common bile duct obstruction resulting in obstructive jaundice Celiac disease Crohn's disease Benign pancreatic conditions Bowel obstruction Surgically altered bowel anatomy

Heffernan N, Cella D, Webster K, Odom L, Martone M, Passik S, Bookbinder M, Fong Y, Jarnagin W, Blumgart L. Measuring health-related quality of life in patients with hepatobiliary cancers: the functional assessment of cancer therapy-hepatobiliary questionnaire. J Clin Oncol. 2002 May 1;20(9):2229-39. doi: 10.1200/JCO.2002.07.093.

Perez MM, Newcomer AD, Moertel CG, Go VL, Dimagno EP. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer. 1983 Jul 15;52(2):346-52. doi: 10.1002/1097-0142(19830715)52:23.0.co;2-z.

Partelli S, Frulloni L, Minniti C, Bassi C, Barugola G, D'Onofrio M, Crippa S, Falconi M. Faecal elastase-1 is an independent predictor of survival in advanced pancreatic cancer. Dig Liver Dis. 2012 Nov;44(11):945-51. doi: 10.1016/j.dld.2012.05.017. Epub 2012 Jun 28.

Sikkens EC, Cahen DL, de Wit J, Looman CW, van Eijck C, Bruno MJ. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol. 2014 May-Jun;48(5):e43-6. doi: 10.1097/MCG.0b013e31829f56e7.

Dutta SK, Rubin J, Harvey J. Comparative evaluation of the therapeutic efficacy of a pH-sensitive enteric coated pancreatic enzyme preparation with conventional pancreatic enzyme therapy in the treatment of exocrine pancreatic insufficiency. Gastroenterology. 1983 Mar;84(3):476-82.

Valerio D, Whyte EH, Schlamm HT, Ruggiero JA, Blackburn GL. Clinical effectiveness of a pancreatic enzyme supplement. JPEN J Parenter Enteral Nutr. 1981 Mar-Apr;5(2):110-4. doi: 10.1177/0148607181005002110.

Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut. 1998 Jan;42(1):92-6. doi: 10.1136/gut.42.1.92.

Delchier JC, Vidon N, Saint-Marc Girardin MF, Soule JC, Moulin C, Huchet B, Zylberberg P. Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations. Aliment Pharmacol Ther. 1991 Aug;5(4):365-78. doi: 10.1111/j.1365-2036.1991.tb00040.x.

Ghaneh P, Neoptolemos JP. Exocrine pancreatic function following pancreatectomy. Ann N Y Acad Sci. 1999 Jun 30;880:308-18. doi: 10.1111/j.1749-6632.1999.tb09534.x.

DiMagno EP, Malagelada JR, Go VL. The relationships between pancreatic ductal obstruction and pancreatic secretion in man. Mayo Clin Proc. 1979 Mar;54(3):157-62.

Graham DY. An enteric-coated pancreatic enzyme preparation that works. Dig Dis Sci. 1979 Dec;24(12):906-9. doi: 10.1007/BF01311943.

Halgreen H, Pedersen NT, Worning H. Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Scand J Gastroenterol. 1986 Jan;21(1):104-8. doi: 10.3109/00365528609034631.

Lankisch PG, Lembcke B, Goke B, Creutzfeldt W. Therapy of pancreatogenic steatorrhoea: does acid protection of pancreatic enzymes offer any advantage? Z Gastroenterol. 1986 Dec;24(12):753-7.

Schneider MU, Knoll-Ruzicka ML, Domschke S, Heptner G, Domschke W. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhoea in chronic pancreatitis. Hepatogastroenterology. 1985 Apr;32(2):97-102.

Nouisa-Arvanitakis S, Stapleton FB, Linshaw MA, Kennedy J. Therapeutic approach to pancreatic extract-induced hyperuricosuria in cystic fibrosis. J Pediatr. 1977 Feb;90(2):302-5. doi: 10.1016/s0022-3476(77)80657-4.

Gullo L, Pezzilli R, Gaiani S. Tolerability and safety of the long-term administration of pancreatic extracts. Pancreas. 1997 Mar;14(2):210-2. doi: 10.1097/00006676-199703000-00018. No abstract available.

Seiler CM, Izbicki J, Varga-Szabo L, Czako L, Fiok J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, Friess H. Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther. 2013 Apr;37(7):691-702. doi: 10.1111/apt.12236. Epub 2013 Feb 5.

Ramesh H, Reddy N, Bhatia S, Rajkumar JS, Bapaye A, Kini D, Kalla M, Thorat V. A 51-week, open-label clinical trial in India to assess the efficacy and safety of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Pancreatology. 2013 Mar-Apr;13(2):133-9. doi: 10.1016/j.pan.2013.01.009. Epub 2013 Feb 5.

Gubergrits N, Malecka-Panas E, Lehman GA, Vasileva G, Shen Y, Sander-Struckmeier S, Caras S, Whitcomb DC. A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. Aliment Pharmacol Ther. 2011 May;33(10):1152-61. doi: 10.1111/j.1365-2036.2011.04631.x. Epub 2011 Mar 21.