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

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Patients 18-100 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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Jacksonville, Fla.

Mayo Clinic principal investigator

Massimo Raimondo, M.D.

Closed for enrollment

More information

Publications

  • Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. Read More on PubMed
  • The relationship between prognosis of advanced pancreatic cancer and exocrine secretion impairment is unknown. Read More on PubMed
  • Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Read More on PubMed
  • This is the first report on the development and initial validation of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire, a 45-item self-report instrument designed to measure health-related quality of life (HRQL) in patients with hepatobiliary cancers. The FACT-Hep consists of the 27-item FACT-G, which assesses generic HRQL concerns, and the newly validated 18-item Hepatobiliary Subscale (HS), which assesses disease-specific issues. Read More on PubMed
  • Pancreatic exocrine insufficiency can follow major pancreatic resection and result in the malabsorption of fat, causing symptoms of steatorrhea, abdominal pain and weight loss. The extent of malabsorption will depend on the original disease process and the type and extent of surgical resection. The steatorrhea can be severe and difficult to control, and patients may require high doses of pancreatic enzyme supplements. There have been few studies that have looked at the treatment of steatorrhea postpancreatectomy, and very few randomized studies. Results of the latter have demonstrated that after treatment with oral pancreatic supplements over a third of postpancreatectomy patients still have significant levels of steatorrhea. These results show that even using the best available agents the complete elimination of steatorrhea following major pancreatic resection is not possible at the present time. This indicates a need for further effective therapies. Read More on PubMed
  • Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea. This may contribute to the profound weight loss that often occurs in these patients. Read More on PubMed
  • The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying. Read More on PubMed
  • Pancreatic enzyme replacement may fail to achieve a beneficial effect because of enzyme inactivation by gastric acid. In this controlled randomized study, 8 hospitalized patients with severe exocrine pancreatic insufficiency and considerable steatorrhoea (greater than 15 g faecal fat/day) were treated with a conventional pancreatic enzyme preparation (Pankreon 700; 3 X 3 dragees daily), with (300 mg) and without cimetidine before meals, and with a new pH-sensitive enzyme preparation (Kreon; 3 X 6 capsules daily) comprising acid-protected granules. Both conventional enzyme replacement plus cimetidine, and acid-protected pancreatin were significantly (p less than 0.05) more effective than conventional enzyme therapy alone. Since both regimens are equally potent in overcoming gastric acid-induced enzyme inactivation, it is concluded that therapy with acid-protected pancreatin may simplify and improve treatment of exocrine pancreatic insufficiency in the presence of gastric hyper- or normo-acidity. Read More on PubMed
  • The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy. Read More on PubMed
  • The therapeutic effectiveness of a conventional (Pankreon-Granulat) and an acid-protected (Kreon) porcine pancreatic enzyme preparation, and an acid-stable fungal enzyme preparation (Nortase) in the treatment of severe pancreatogenic steatorrhoea was investigated. The study comprised 17 patients with chronic pancreatitis and exocrine pancreatic insufficiency with (A) or without (B) a previous Whipple's procedure (B II resection + partial duodenopancreatectomy). With all three enzyme preparations, a significant (p less than 0.05) reduction in the total faecal fat excretion/day was achieved. In therapy group A, this reduction was, on average, 58% for Kreon (100,000 U lipase/day), 67% for Pankreon-Granulat (360,000 U lipase/day) and 54% for Nortase (75,000 U lipase/day), the respective figures for therapy group B being 58%, 52% and 46% at identical dosages. Thus, in both groups, the effect produced by the conventional porcine pancreatic enzyme preparation and the acid-protected porcine or the acid-stable fungal enzyme preparation was largely equivalent, although the latter two preparations were administered at only 1/4 of the dosages of the former preparation. On the basis of the respective average reduction in total faecal fat excretion and average number of stools/day, it would appear that in patients with chronic pancreatitis and prior Whipple's procedure, Pankreon-Granulat should be administered for enzyme replacement while in patients with an intact upper gastrointestinal tract, Kreon should be administered, in the treatment of steatorrhoea in chronic pancreatitis. Read More on PubMed
  • In 12 patients with biopsy-proven pancreatic ductal adenocarcinoma, the following were determined: (1) whether decreased food intake, malabsorption, or altered fat metabolism were associated with weight loss; (2) the effect of pancreatic extract as treatment for malabsorption; and (3) the accuracy of the triolein breath test for detection of steatorrhea. Weight loss occurred in 11 patients and only in patients who had either malabsorption (n = 5), low coefficients of caloric consumption (n = 2), or both (n = 4). Nine patients had fat malabsorption, six had protein malabsorption, and caloric consumption was decreased in seven patients. Metabolism of oleic acid was significantly decreased (P less than 0.01) compared to normal subjects and correlated with basal metabolic rates (r = 0.6; P less than 0.05) which were within the range of normal values for age and sex. Body weight loss correlated only with coefficients of fat and protein absorption (r = 0.59; P less than 0.05). Treatment of patients with pancreatic extract resulted in significant improvement in absorption in those with moderate to severe fat or protein malabsorption (coefficient of absorption less than 80%) but no significant improvement occurred in patients with mild fat or protein malabsorption. The triolein breath test was abnormal in all patients with fat malabsorption and predicted improvement of fat absorption in five of six patients with steatorrhea who were treated with pancreatic extract. Thus, in pancreatic cancer, weight loss is associated with malabsorption; exogenous pancreatic extract significantly improves moderate to severe fat or protein malabsorption, and the triolein breath test detects fat malabsorption and predicts the treatment response to pancreatic extract. Read More on PubMed
  • The therapeutic efficacy of a pH-sensitive enteric coated pancreatic enzyme preparation was compared with conventional pancreatic enzyme preparations in 6 adult patients with exocrine pancreatic insufficiency. Fecal fat excretion and postprandial duodenal recovery of orally ingested pancreatic enzymes were evaluated after ingestion of each preparation. Fecal fat excretion decreased significantly (p less than 0.005) on treatment with pH-sensitive and conventional pancreatic enzyme preparations. Postprandial concentration and delivery of trypsin and lipase in samples aspirated from duodenojejunal junction were higher after ingestion of conventional pancreatic enzyme preparation as compared to the pH-sensitive enteric coated preparation. The difference, however, did not reach statistical significance. Our observations suggest that the pH-sensitive enteric coated pancreatic enzyme preparation is only as effective as conventional pancreatic enzyme preparations in controlling fat malabsorption in patients with exocrine pancreatic insufficiency. Failure of pH-sensitive enteric coated preparation to deliver greater quantities of pancreatic enzymes at duodenojejunal junction is most likely related to the impaired release of enzymes from microspheres due to low intraluminal pH in the upper small intestine in pancreatic insufficiency. Read More on PubMed
  • A new enteric-coated pancreatic enzyme preparation (microspheres) was compared with traditional enzyme tablets in six subjects with severe exocrine pancreatic insufficiency. The microspheres were found to be as effective as traditional enzyme supplements. In most patients in balance studies, the lowest fecal fat values were obtained with microsphere therapy in spite of a smaller amount of lipase administered (6015 vs 10,800-43,200 lipase units per meal). In contrast to enteric-coated tablets, microspheres can be recommended in the treatment of pancreatic steatorrhea. Read More on PubMed
  • Precise relationships between pancreatic ductal obstruction and pancreatic secretory capacity have not been established. In this study, we describe the quantitative relationships between the lengths of opacified ducts obtained at retrograde pancreatography and the secretory capcity of the gland for volume, bicarbonate, lipase, and trypsin. Forty-five patients (17 with pancreatic cancer, 6 pancreatitis, 5 other malignancies, and 17 nonmalignant, nonpancreatic disease found at laparotomy) were studied with a method of duodenal intubation and perfusion with basal saline perfusion alone or with continuous intravenous infusion of secretin or of cholecystokinin-pancreozymin. Secretory outputs of volume, bicarbonate, and enzymes compared with the length of opacified ducts showed a significant (P less than 0.05) linear relationship for patients with pancreatic cancer, pancreatitis, and other cancers. The resulting data imply that obstruction of the pancreatic duct is important in decreasing secretion of the pancreas in pancreatic disease. The relationship between obstruction and pancreatic secretion demonstrates that a decrease in exocrine pancreatic secretion cannot be detected until more than 60% of the total length of the main pancreatic duct has been obstructed. Read More on PubMed
  • The relationship between the dosage of pancreatic extract and the excretion of uric acid was investigated in 29 patients with cystic fibrosis and exocrine pancreatic insufficiency. Urinary excretion of uric acid was normal in patients receiving small doses of pancreatic extracts and abnormally high in those receiving large amounts. In the latter group, normouricosuria was achieved by reducing the dose of pancreatic extract. Normal stool patterns and adequate weight gains were preserved by a diet modification that was well accepted by the patients. To eliminate the potential renal consequences of hyperuricosuria, it seems appropriate to control the need for increasing amounts of pancreatic enzymes by limiting the dietary intake of fat and maintaining a positive caloric and nitrogen balance with high intake of protein and carbohydrates and supplementation with medium-chain triglycerides. Read More on PubMed
  • In 23 adult patients with pancreatic insufficiency, we evaluated the efficacy of a pancreatic enzyme delivered as pH-sensitive enteric-coated pancreatic lipase microspheres, and compared it with placebo and other available enzyme supplements. In a short-term study, fecal fat was 23.5 +/- 7 g/day with the microspheres, compared with 29.9 +/- 8 with other supplements, providing fat utilization of 76 +/- 7% versus 63 +/- 10% (p less than 0.05). Microspheres reduced daily stool frequency to 1.9 movements from 4.3 on other enzymes (p less than 0.01). These results were obtained with an average intake of 10 microsphere capsules/day. In a year-long study of 22 patients, an average weight gain of 4.0 +/- 1.1 kg was observed associated with return of near-normal social and work life-style in previously housebound patients. Read More on PubMed
  • In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. Read More on PubMed
  • To assess the efficacy and safety of pancreatin (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis (CP). Read More on PubMed

Study Results Summary

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CLS-20506023

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