Lubiprostone is a locally acting chloride channel activator with a similar mechanism of action to bulking agents and osmotic laxatives on intestinal fluid. Lubiprostone increases intestinal fluid volume and motility, resulting in stool softening and ease of passage. Although the U.S. Food and Drug Administration approved the use of lubiprostone in January 2006 for chronic idiopathic constipation, no studies in patients with cancer have been published.
Baker, D.E. (2007). Lubiprostone: A new drug for the treatment of chronic idiopathic constipation. Reviews in Gastroenterological Disorders, 7, 214–222.
In phase III, placebo-controlled studies, lubiprostone 24 mcg twice daily was compared to placebo. Studies 1, 2, and 3 comprised a two-week drug-free period followed by treatment with lubiprostone 24 mcg twice daily for four weeks, followed by randomization to continue lubiprostone or placebo.
Open-label studies used lubiprostone 24 mcg twice daily. Three studies of long-term clinical safety assessed lubiprostone administered for 12 months in patients with chronic idiopathic constipation.
Phase III Studies
Study 1 and 2
Placebo-controlled RCTs demonstrated lubiprostone was well tolerated and not associated with severe adverse effects. However, incidence of nausea was higher. Comparative studies with other therapies are needed.
Barish, C.F., Drossman, D., Johanson, J.F., & Ueno, R. (2010). Efficacy and safety of lubiprostone in patients with chronic constipation. Digestive Diseases and Sciences, 55, 1090–1097.
To assess the efficacy and safety of lubiprostone in the treatment of patients with chronic constipation.
Patients had a washout period, followed by a two-week prerandomization period. Patients were randomized to receive either oral lubiprostone 24-mcg capsules (n = 119) or placebo (n = 118) twice daily with food and at least 8 oz of water. Patients were instructed to keep daily diaries to record their medication administration, use of medication rescues, and occurrences of bowel movements (BMs) (date and time). Study assessments were scheduled after one week (office visits), two weeks (telephone evaluation), four weeks (end-of-treatment office visit), and two weeks following the end of treatment.
This was a randomized, double-blinded, placebo-controlled study.
Lubiprostone was an effective treatment for chronic constipation.
Lubiprostone has been shown to be effective in the management of chronic constipation and is used for patients with chronic constipation related to irritable bowel syndrome. However, additional studies are warranted in patients with cancer, as well as the palliative care population, in which patients are receiving chemotherapy agents, antiemetics, and narcotics that contribute to their constipation.
Johanson, J.F., Morton, D., Geenen, J., & Ueno, R. (2008). Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. American Journal of Gastroenterology, 103, 170–177.
To assess the efficacy and safety of lubiprostone 24 mcg BID in patients with chronic constipation.
Patients were randomized to receive either oral lubiprostone 24-mcg capsules or placebo capsules. Patients continued to record information regarding bowel movements (BMs), use of rescue medications, and symptoms on a daily basis. Study drug capsules were counted to assess compliance every two weeks. Rescue medication comprised bisacodyl suppository and fleet enema if the suppository was not effective. Efficacy was defined as the frequency of spontaneous BMs during the first and subsequent study weeks. Patients were followed for four weeks.
This was a double-blind, placebo-controlled randomized trial.
Taking lubiprostone improved frequency of spontaneous BMs and constipation-related symptoms, with low incidence of treatment-related adverse events.
Lubiprostone effectively improved constipation in this study; however, applicability to patients with cancer is not clear. Nausea was the most common side effect, which could limit its use in patients with cancer, who may be on other medications and treatments that also cause nausea. Research involving patients with cancer-related constipation should be considered.