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Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial—JORTC-PAL08 (DIRECT) study

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Abstract

Purpose

Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP.

Methods

Patients (N = 70) with CNP unresponsive to or intolerant of opioid–pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables.

Results

Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046).

Conclusion

Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

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Abbreviations

CNP Cancer neuropathic pain:

NP Neuropathic pain

IASP International Association for the Study of Pain

BPI-SF item 5 Brief pain inventory item 5

CIPN Chemotherapy-induced peripheral neuropathy

HADS Hospital anxiety and depression scale

JORTC Japanese Organization for Research and Treatment of Cancer

PCS Pain catastrophizing scale

SF-MPQ Short-form McGill pain questionnaire

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Acknowledgments

This work was supported by the following grants: Sasakawa Memorial Health Foundation Research Grant (Grant No.: 2013-A003), 2014-2017 Grant-in-Aid for Scientific Research (Grant-in-Aid for Young Scientists B; Grant No.: 26860486), 2014 Health Labour Sciences Research Grant (Grant for Innovative Clinical Cancer Research: H26-Innovative Cancer-General-056; Grant No.: 16ck0106059h0003), 2015-2016 Japan Agency for Medical Research and Development (AMED) award (Innovative Clinical Cancer Research; Grant No.: 17ck0106328h0001), and a 2017 Japan Agency for Medical Research and Development (AMED) award (Innovative Clinical Cancer Research; Grant No.: 18ck0106328h0002).

The authors thank in advance all the patients, investigators, and institutions involved in this study.

Author information

Authors and Affiliations

  1. Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, Osaka, Japan

    Hiromichi Matsuoka, Kiyohiro Sakai, Miki Nakura & Atsuko Koyama

  2. Palliative Care Center, Kindai University Faculty of Medicine, Osaka, Japan

    Hiromichi Matsuoka, Kiyohiro Sakai & Atsuko Koyama

  3. Faculty of Health, University of Technology Sydney, Sydney, Australia

    Hiromichi Matsuoka

  4. Department of Palliative Medicine, University of Saitama Medical University, Saitama, Japan

    Satoru Iwase

  5. Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tempei Miyaji

  6. Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Takashi Kawaguchi

  7. Japanese Organization for Research and Treatment of Cancer (JORTC), JORTC Data Center, Tokyo, Japan

    Keisuke Ariyoshi & Shunsuke Oyamada

  8. Department of Palliative Medicine, National Cancer Center Hospital, Tokyo, Japan

    Eriko Satomi & Hiroto Ishiki

  9. Department of Psychosomatic Internal Medicine, Kansai Medical University, Osaka, Japan

    Hideaki Hasuo & Hiroko Sakuma

  10. Department of Psychosomatic Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan

    Akihiro Tokoro & Yoshinobu Matsuda

  11. Yamanobe General Hospital Internal medicine, Nara, Japan

    Kazuki Tahara

  12. Department of Palliative Medicine, National Kyushu Cancer Center, Fukuoka, Japan

    Hiroyuki Otani

  13. Itami Seifu Hospital Internal medicine, Hyogo, Japan

    Yoichi Ohtake

  14. Nagoya University Hospital, Aichi, Japan

    Hiroaki Tsukuura

  15. Department of Palliative Medicine, National Cancer Center East, Kashiwa, Japan

    Yoshihisa Matsumoto

  16. Department of Medical Oncology, Izumi City General Hospital, Izumi, Japan

    Yoshikazu Hasegawa

  17. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan

    Yuki Kataoka

  18. Department of Palliative Medicine, Kindai University Nara Hospital, Nara, Japan

    Masatomo Otsuka

  19. Palliative and Supportive Care Division, Seirei Mikatahara General Hospital, Hamamatsu, Japan

    Tatsuya Morita

  20. Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takuhiro Yamaguchi

Authors
  1. Hiromichi Matsuoka
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  2. Satoru Iwase
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  3. Tempei Miyaji
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  4. Takashi Kawaguchi
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  7. Eriko Satomi
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  16. Hiroaki Tsukuura
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Contributions

HM, SI, TM, TK, KA, SO, HI, YM, TM, TY, and AK participated in the design of the study.

HM, HI, ES, HH, HS, AT, YM, KT, HO, YO, HT, YM, YH, YK, MO, KS, MN, and AK conducted the study.

TM, KA, SO, and TY analyzed the data.

HM, HI, YK, TM, and TY wrote the paper.

All authors contributed to writing and revising the manuscript critically, and all gave their final approval of the version to be published.

Corresponding author

Correspondence to Hiromichi Matsuoka.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval

The protocol was approved by the institutional review board of each study site.

Statement of informed consent

Informed consent for participation in the trial was obtained from all patients.

Sponsor detail

Sasakawa Health Foundation

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Phone: 81-3-6229-5377

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Phone: 81-3-5253-4111

Ministry of Health, Labour and Welfare

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Minato-ku,Tokyo 107-0052, Japan

Phone: 81-3-5253-1111

Japan Agency for Medical Research and Development

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Matsuoka, H., Iwase, S., Miyaji, T. et al. Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial—JORTC-PAL08 (DIRECT) study. Support Care Cancer 28, 2931–2939 (2020). https://doi.org/10.1007/s00520-019-05138-9

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