Current Oncology Reports

, Volume 9, Issue 4, pp 278–284 | Cite as

Cancer-related constipation



Cancer-related constipation is common and a significant detractor from patient quality of life. It has many possible causes and is still not well understood. Information is lacking on therapies for cancer-related constipation among current medications approved by the US Food and Drug Administration (FDA). Most agents have only been formally tested in comparison with placebo in chronic idiopathic constipation if at all. Few comparative studies of laxatives have been performed to establish superiority or synergy. As we understand more about the physiology of the gastrointestinal tract, new targeted therapies have become available. These include a selective chloride channel activator, lubiprostone, and a selective 5HT4 serotonin receptor agonist, tegaserod, both of which have been FDA approved for chronic idiopathic constipation. The role of these agents in cancer-related constipation remains to be seen. On the horizon are two investigational peripherally acting opioid receptor antagonists, alvimopan and methylnaltrexone. Preliminary results in cancer-related constipation suggest that these agents may be important additions to our treatment repertoire.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Longstreth GF, Thompson WG, Chey WD, et al.: Functional bowel disorders. Gastroenterology 2006, 130:1480–1491.PubMedCrossRefGoogle Scholar
  2. 2.
    Brandt LJ, Prather CM, Quigley EM, et al.: Systematic review on the management of chronic constipation in North America. Am J Gastroenterol 2005, 100(Suppl 1):S5–S21.PubMedCrossRefGoogle Scholar
  3. 3.
    Sykes NP: The pathogenesis of constipation. J Support Oncol 2006, 4:213–218.PubMedGoogle Scholar
  4. 4.
    Sykes NP: The relationship between opioid use and lax ative use in terminally ill cancer patients. Palliat Med 1998, 12:375–382.PubMedCrossRefGoogle Scholar
  5. 5.
    Gomes OA, de Souza RR, Liberti EA: A preliminary investigation of the effects of aging on the nerve cell number in the myenteric ganglia of the human colon. Gerontology 1997, 43:210–217.PubMedCrossRefGoogle Scholar
  6. 6.
    Garvey M, Noyes R, Jr., Yates W: Frequency of constipation in major depression: relationship to other clinical variables. Psychosomatics 1990, 31:204–206.PubMedGoogle Scholar
  7. 7.
    Fenn GC, Wilkinson PD, Lee CE, Akbar FA: A general practice study of the efficacy of Regulan in functional constipation. Br J Clin Pract 1986, 40:192–197.PubMedGoogle Scholar
  8. 8.
    Ashraf W, Park F, Lof J, Quigley EM: Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation. Aliment Pharmacol Ther 1995, 9:639–647.PubMedCrossRefGoogle Scholar
  9. 9.
    Moriarty KJ, Kelly MJ, Beetham R, Clark ML: Studies on the mechanism of action of dioctyl sodium sulphosuccinate in the human jejunum. Gut 1985, 26:1008–1013.PubMedGoogle Scholar
  10. 10.
    Sykes NP: A volunteer model for the comparison of laxatives in opioid-related constipation. J Pain Symptom Manage 1996, 11:363–369.PubMedCrossRefGoogle Scholar
  11. 11.
    Sanders JF: Lactulose syrup assessed in a double-blind study of elderly constipated patients. J Am Geriatr Soc 1978, 26:236–239.PubMedGoogle Scholar
  12. 12.
    Wesselius-De Casparis A, Braadbaart S, et al.: Treatment of chronic constipation with lactulose syrup: results of a double-blind study. Gut 1968, 9:84–86.PubMedGoogle Scholar
  13. 13.
    Andorsky RI, Goldner F: Colonic lavage solution (polyethylene glycol electrolyte lavage solution) as a treatment for chronic constipation: a double-blind, placebo-controlled study. Am J Gastroenterol 1990, 85:261–265.PubMedGoogle Scholar
  14. 14.
    DiPalma JA, DeRidder PH, Orlando RC, et al.: A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol 2000, 95:446–450.PubMedCrossRefGoogle Scholar
  15. 15.
    Gremse DA, Hixon J, Crutchfield A: Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children. Clin Pediatr (Phila) 2002, 41:225–229.CrossRefGoogle Scholar
  16. 16.
    Soffer EE, Metcalf A, Launspach J: Misoprostol is effective treatment for patients with severe chronic constipation. Dig Dis Sci 1994, 39:929–933.PubMedCrossRefGoogle Scholar
  17. 17.
    Roarty TP, Weber F, Soykan I, McCallum RW: Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial. Aliment Pharmacol Ther 1997, 11:1059–1066.PubMedCrossRefGoogle Scholar
  18. 18.
    Verne GN, Davis RH, Robinson ME, et al.: Treatment of chronic constipation with colchicine: randomized, double-blind, placebo-controlled, crossover trial. Am J Gastroenterol 2003, 98:1112–1116.PubMedGoogle Scholar
  19. 19.
    Lyden-Sokolowski A, Nilsson A, Sjoberg P: Two-year carcinogenicity study with sennosides in the rat: emphasis on gastro-intestinal alterations. Pharmacology 1993, 47Suppl 1:209–215.PubMedCrossRefGoogle Scholar
  20. 20.
    Mitchell JM, Mengs U, McPherson S, et al.: An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat. Arch Toxicol 2006, 80:34–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Ueno R, Osama H, Habe T, et al.: Oral SPI-0211 increases intestinal fluid secretion and chloride concentration without altering serum electrolyte levels Gastroenterology 2004, 126:A298 (abstract M1109).Google Scholar
  22. 22.
    Camilleri M, Bharucha AE, Ueno R, et al.: Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 2006, 290:G942–G947.PubMedCrossRefGoogle Scholar
  23. 23.
    Johanson J, Gargano M, Holland P, et al.: Phase III study of lubiprostone, a chloride channel-2 (ClC-2) activator for the treatment of constipation: safety and primary efficacy [abstract]. Am J Gastroenterol 2005, 100:s328–s329.Google Scholar
  24. 24.
    Johanson J, Gargano M, Holland P, et al.: Phase III efficacy and safety of RU-0211, a novel chloride channel activator, for the treatment of constipation Gastroenterology 2003, 124:A48.CrossRefGoogle Scholar
  25. 25.
    Johanson JF, Wald A, Tougas G, et al.: Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial. Clin Gastroenterol Hepatol 2004, 2:796–805.PubMedCrossRefGoogle Scholar
  26. 26.
    Kamm MA, Muller-Lissner S, Talley NJ, et al.: Tegaserod for the treatment of chronic constipation: a randomized, double-blind, placebo-controlled multinational study. Am J Gastroenterol 2005, 100:362–372.PubMedCrossRefGoogle Scholar
  27. 27.
    Muller-Lissner SA, Fumagalli I, Bardhan KD, et al.: Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001, 15:1655–1666.PubMedCrossRefGoogle Scholar
  28. 28.
    Novick J, Miner P, Krause R, et al.: A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2002, 16:1877–1888.PubMedCrossRefGoogle Scholar
  29. 29.
    Kellow J, Lee OY, Chang FY, et al.: An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut 2003, 52:671–676.PubMedCrossRefGoogle Scholar
  30. 30.
    Gonenne J, Camilleri M, Ferber I, et al.: Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol 2005, 3:784–791.PubMedCrossRefGoogle Scholar
  31. 31.
    Yuan CS, Doshan H, Charney MR, et al.: Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans. J Clin Pharmacol 2005, 45:538–546.PubMedCrossRefGoogle Scholar
  32. 32.
    Paulson DM, Kennedy DT, Donovick RA, et al.: Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction—a 21-day treatment-randomized clinical trial. J Pain 2005, 6:184–192.PubMedCrossRefGoogle Scholar
  33. 33.
    Yuan CS, Foss JF, O’Connor M, et al.: Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial. JAMA 2000, 283:367–372.PubMedCrossRefGoogle Scholar
  34. 34.
    Thomas J, Lipman A, Slatkin N, et al.: A phase III double-blind, placebo-controlled trial of methylnaltrexone (MNTX) for opioid-induced constipation (OIC) in advanced medical illness (AMI). J Clin Oncol 2005, 23(16S):1096s.Google Scholar
  35. 35.
    Slatkin N, Karver S, Thomas J, et al.: A phase III double-blind, placebo-controlled trial of every other day dosing of methylnaltrexone for opioid-induced constipation in advanced illness. Gastroenterology 2006, 131:950.CrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.San Diego Hospice & Palliative Care, San DiegoSan DiegoUSA

Personalised recommendations