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Assessment of gastrointestinal function and response to megesterol acetate in subjects with gastrointestinal cancers and weight loss

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Abstract

Background

Cancer-associated anorexia/cachexia syndrome (CACS) is common in advanced gastrointestinal malignancies and felt to be due primarily to cytokine-induced appetite suppression. Therapy with an appetite stimulant (megesterol acetate) is commonly employed, but results are sometimes disappointing. We hypothesize that CACS not only suppresses appetite but also interferes with gastrointestinal function.

Methods

We conducted a prospective study in which 21 subjects with advanced gastrointestinal cancer and weight loss had digestive function. Patients were assessed using an indirect stable isotope method, and nutritional parameters were determined following which patients were treated with megesterol acetate for 4 weeks. Nutritional parameters were then reassessed, weight change determined, and the results were correlated with digestive function results obtained at the initiation of the study.

Results

Abnormal gastrointestinal function based on the stable isotope test was common (86% of patients). The majority of the abnormal function appeared to be due to abnormal pancreatic function testing, in which 17/21 subjects recorded low results. Initial albumin, prealbumin, and carotene values were also frequently abnormal (55–65% of patients). Megesterol acetate therapy resulted in a weight gain in most (75%) patients, although serum albumin fell modestly in the group (average decrease of 0.2 mg/dl). However, prealbumin levels rose in 70% and carotene levels rose in 55%. The degree of weight gain was negatively correlated with previous self-reported weight loss (r=−0.53, p<0.05), and positively correlated (p<0.05) with pretherapy carotene (r=0.58), prealbumin (r=0.61) and the pancreatic function (digestive) phase of the digestive function test (r=0.41).

Conclusion

These data suggest that abnormal digestive function is commonly seen in subjects with CACS and advanced gastrointestinal cancer, and that both pretherapy digestive function and nutritional status can predict or possibly influence the outcome of hormonal appetite stimulation therapy.

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References

  1. Beller E, Tattersall M, Lumley T, Levi J, Dalley D, Olver I, Page J, Abdi E, Wynne C, Friedlander M, Boadle D, Wheeler H, Margrie S, Simes RJ (1997) Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group. Ann Oncol 8:277–283

    Article  CAS  PubMed  Google Scholar 

  2. Bragelmann R, Armbrecht U, Resemeyer D, Schneider B, Zilly W, Stockbrugger RW (1996) Nutrient malassimilation following total gastrectomy. Scan J Gastroenterol [Suppl] 218:26–33

    Google Scholar 

  3. Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ (1998) Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 42:92–96

    CAS  PubMed  Google Scholar 

  4. Bruno MJ, Hoek FJ, Delzenne B, van Leeuwen DJ, Schteingart CD, Hafmann AF, Tytgat GN (1995) Simultaneous assessments of exocrine pancreatic function by cholestryl-[14C]octanoate breath test and measurement of plasma p-aminobenzoic acid. Clin Chem 41:599–604

    CAS  PubMed  Google Scholar 

  5. Burrowes JD, Bluestone PA, Wang J. Pierson RN Jr (1999) The effects of moderate doses of megestrol acetate on nutritional status and body composition in a hemodialysis patient. J Ren Nutr 9:89–94

    CAS  PubMed  Google Scholar 

  6. Caras S, Laurie S, Cronk W, Tompkins W, Brashear R, McCallum RW (1996) Case report: pancreatic cancer presenting with paraneoplastic gastroparesis. Am J Med Sci 312:34–36

    Article  CAS  PubMed  Google Scholar 

  7. Carlson SJ, Deutsch JC, Craig RM (1998) Physiologic response to a protein, carbohydrate, fat meal in patients with immunodeficiency virus who underwent small intestinal enteropathy as characterized by a kinetic model of D-xylose absorption. JPEN J Parenter Enteral Nutr 22:27–30

    CAS  PubMed  Google Scholar 

  8. Craig RM, Atkinson AJ Jr (1988) D-xylose testing: a review. Gastroenterology 95:223–231

    CAS  PubMed  Google Scholar 

  9. Craig RM, Ehrenpreis ED (1999) D-xylose testing. J Clin Gastroenterol 29:143–150

    Article  CAS  PubMed  Google Scholar 

  10. Davis MP (2002) New drugs for the anorexia-cachexia syndrome. Curr Oncol Rep 4:264–274

    PubMed  Google Scholar 

  11. Deutsch JC, Santhosh-Kumar CR, Kolli VR (1995) A noninvasive stable-isotope method to simultaneously assess pancreatic exocrine function and small bowel absorption. Am J Gastroenterol 12:2182–2185

    Google Scholar 

  12. Deutsch JC (1998) Normal digestive physiology and the evaluation of digestive function. Semin Oncol 2 [Suppl 6]:4–11

  13. Ghaneh P, Neoptolemos JP (1999) Exocrine pancreatic function following pancreatectomy. Ann NY Acad Sci 880:308–318

    Google Scholar 

  14. Harte C, Henry MT, Murphy KD, Mitchell TH (1995) Progestogens and Cushing’s syndrome. Ir J Med Sci 164:274–275

    CAS  PubMed  Google Scholar 

  15. Hoek FJ, van den Bergh FA, Lein Elhorst JT, Meiher JL, Timmer E, Tytgat GN (1987) Improved specificity of the PABA test with p-aminosalicylic acid (PAS). Gut 28:468–473

    CAS  PubMed  Google Scholar 

  16. Kataoka K, Yamane Y, Kato M, Kashima K (1997) Diagnosis of chronic pancreatitis using noninvasive tests of exocrine pancreatic function—comparison to duodenal intubation tests. Pancreas 15:409–415

    CAS  PubMed  Google Scholar 

  17. Lautenbach E, Lichtenstein GR (1995) Retroperitoneal leiomyosarcoma and gastroparesis: a new association and review of tumor-associated intestinal pseudo-obstruction. Am J Gastroenterol 90:1338–1341

    CAS  PubMed  Google Scholar 

  18. Lelli G, Montanari M, Gilli G, Scapoli D, Antonietti C, Scapoli D (2003) Treatment of the cancer anorexia-cachexia syndrome: a critical reappraisal. J Chemother 15:220–225

    CAS  PubMed  Google Scholar 

  19. Mantovani G, Maccio A, Lai P, Massa E, Ghiani M, Santona MC (1998) Cytokine involvement in cancer anorexia/cachexia: role of megesterol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9:99–106

    CAS  PubMed  Google Scholar 

  20. Mantovani G, Maccio A, Lai P, Massa E, Ghiani M, Santona MC (1998) Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate. Semin Oncol 25:45–52

    Google Scholar 

  21. Mc Millan DC, O’Gorman P, Fearon KC, McArdle CS (1997) A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancer patients. Br J Cancer 76:788–790

    PubMed  Google Scholar 

  22. McMillan DC, Wigmore SJ, Fearon KC, O’Gorman P, Wright CE, McArdle CS (1999) A prospective randomized study of megesterol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer 79:495–500

    Article  CAS  PubMed  Google Scholar 

  23. Mee AS, Girdwood AH, Walker E, Gilinsky NH, Kottler RE, Marks IN (1985) Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis. Gut 26:1257–1262

    CAS  PubMed  Google Scholar 

  24. Meyer BM, Campbell DR, Curington CW, Toskes PP (1987) Bentiromide test is not affected in patients with small bowel or liver disease. Pancreas 2:44–47

    CAS  PubMed  Google Scholar 

  25. Perez De Oteyza C, Garcia Cortes A, Menendex Martinez MA, Torres Leon JM, Perez Aznar C, Carnicero Bujarrabal M (1998) [Megestrol in the treatment of AIDS associated cachexia. Evaluation by bioelectric impedance analysis of body composition]. An Med Interna 15:255–258

    PubMed  Google Scholar 

  26. Selby S (1970) Standard mathematical tables, 18th edn. Chemical Rubber Company, Cleveland, p 610

  27. Smith GM, Chesner IM, Asquith P, Leyland MJ (1990) Small intestinal bacterial overgrowth in patients with chronic lymphocytic leukaemia. J Clin Pathol 43:58–59

    Google Scholar 

  28. Tisdale MJ (2003) Pathogenesis of cancer cachexia. J Support Oncol 1:159–168

    CAS  Google Scholar 

  29. Westman G, Bergman B, Albertsson M, Kadar L, Gustavsson G, Thaning L, Andersson M, Straumits A, Jeppson B, Linden CJ, Ewers SB, Andersson H, Mercke C, Hafstrom L, Birck O, Orgum P (1999) Megesterol acetate in advanced, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomized multicentre trial. Eur J Cancer 35:586–595

    Article  CAS  Google Scholar 

  30. Yeh SS, Wu SY, Lee TP, Olson JS, Stevens MR, Dixon T, Porcelli RJ, Schuster MW (2000) Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: results of a double-blind, placebo-controlled study. J Am Geriatr Soc 48:485–492

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cancer Center, University of Colorado HSC, Denver, CO 80262, USA

    John Deutsch

  2. Section of Gastroenterology, St. Mary’s Duluth Clinic, 400 E 3rd St., Duluth, MN 55805, USA

    John Deutsch

  3. Division of Hematology, UCHSC Hematology, University of Colorado, B170 4200 E 9th Ave., Denver, CO 80262, USA

    J. Fred Kolhouse

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Correspondence to John Deutsch.

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Supported by a grant from Bristol-Meyers Squibb.

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Deutsch, J., Kolhouse, J.F. Assessment of gastrointestinal function and response to megesterol acetate in subjects with gastrointestinal cancers and weight loss. Support Care Cancer 12, 503–510 (2004). https://doi.org/10.1007/s00520-004-0615-4

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  • DOI: https://doi.org/10.1007/s00520-004-0615-4

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