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

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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.

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Data availability

The dataset generated and analyzed during the current study is available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pharmacy, Kochi Medical Hospital School, 185-1 Kohasu, Oko town, Nankoku City, Kochi, Japan

    Kei Kawada, Yasuyo Morita & Mitsuhiko Miyamura

  2. Department of Biomedical Science, Kochi Medical Graduate School, 185-1 Kohasu, Oko town, Nankoku, Kochi, Japan

    Kei Kawada & Mitsuhiko Miyamura

  3. Department of Neurosurgery, Kochi Health Sciences Center, Ike 2125-1,, Kochi City, Kochi, Japan

    Tsuyoshi Ohta

  4. Department of Neurosurgery, Kochi Medical Hospital School, 185-1 Kohasu, Oko town, Nankoku City, Kochi, Japan

    Hitoshi Fukuda

  5. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, Japan

    Toshinobu Hayashi

  6. Pharmaceutical Department, Kochi Health Sciences Center, Ike 2125-1,, Kochi City, Kochi, Japan

    Koudai Tanaka

  7. Department of Hematology, Kochi Health Sciences Center, Ike 2125-1,, Kochi City, Kochi, Japan

    Toshi Imai

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  1. Kei Kawada
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Contributions

Material preparation, data collection, and analysis were performed by Kei Kawada, Tsuyoshi Ohta, and Hitoshi Fukuda. The first draft of the manuscript was written by Kei Kawada, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Kei Kawada.

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The Kochi Health Sciences Center Institutional Review Board approved the study. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent was waived in view of the retrospective nature of the study. Confidentiality and anonymity of patient data was maintained throughout.

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Kawada, K., Ohta, T., Fukuda, H. et al. Effect of lubiprostone on vinca alkaloid–induced constipation in patients with hematological malignancies: a propensity score–matched analysis. Ann Hematol 99, 2429–2436 (2020). https://doi.org/10.1007/s00277-020-04222-z

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