Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis

Ann Hematol. 2020 Oct;99(10):2429-2436. doi: 10.1007/s00277-020-04222-z. Epub 2020 Aug 24.

Abstract

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Keywords: Constipation; Hematological malignancy; Laxatives; Lubiprostone; Propensity score matching; Vinca alkaloids.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chloride Channel Agonists / therapeutic use*
  • Constipation / chemically induced
  • Constipation / drug therapy*
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Evaluation
  • Drug Therapy, Combination
  • Famotidine / therapeutic use
  • Female
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Laxatives / pharmacology
  • Laxatives / therapeutic use
  • Lubiprostone / therapeutic use*
  • Lymphoma / drug therapy*
  • Magnesium Oxide / therapeutic use
  • Male
  • Middle Aged
  • Narcotics / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prednisone / administration & dosage
  • Propensity Score
  • Proton Pump Inhibitors / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Sennosides / therapeutic use
  • Vinca Alkaloids / administration & dosage
  • Vinca Alkaloids / adverse effects*
  • Vincristine / administration & dosage

Substances

  • Antineoplastic Agents, Phytogenic
  • Chloride Channel Agonists
  • Laxatives
  • Narcotics
  • Proton Pump Inhibitors
  • Sennosides
  • Vinca Alkaloids
  • Magnesium Oxide
  • Vincristine
  • Famotidine
  • Lubiprostone
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol