Advertisement

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

  • Hiromichi MatsuokaEmail author
  • Satoru Iwase
  • Tempei Miyaji
  • Takashi Kawaguchi
  • Keisuke Ariyoshi
  • Shunsuke Oyamada
  • Eriko Satomi
  • Hiroto Ishiki
  • Hideaki Hasuo
  • Hiroko Sakuma
  • Akihiro Tokoro
  • Yoshinobu Matsuda
  • Kazuki Tahara
  • Hiroyuki Otani
  • Yoichi Ohtake
  • Hiroaki Tsukuura
  • Yoshihisa Matsumoto
  • Yoshikazu Hasegawa
  • Yuki Kataoka
  • Masatomo Otsuka
  • Kiyohiro Sakai
  • Miki Nakura
  • Tatsuya Morita
  • Takuhiro Yamaguchi
  • Atsuko Koyama
Original Article

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.

Keywords

Duloxetine Neuropathic cancer pain Palliative care Randomized controlled trial Secondary analyses 

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

Notes

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.

Authors’ 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.

Compliance with ethical standards

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

Nippon Foundation Building 5F,1-2-2 Akasaka,

Minato-ku,Tokyo 107-0052, Japan

Phone: 81-3-6229-5377

Fax: 81-3-6229-5388

Health Labour Sciences Research Grant

5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan

Phone: 81-3-5253-4111

Ministry of Health, Labour and Welfare

1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916, Japan

Minato-ku,Tokyo 107-0052, Japan

Phone: 81-3-5253-1111

Japan Agency for Medical Research and Development

22F Yomiuri Shimbun Bldg. 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004 Japan

Minato-ku,Tokyo 107-0052, Japan

Phone: 81-3-6870-2221

Fax: 81-3-6870-2244

References

  1. 1.
    Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14:162–173.  https://doi.org/10.1016/S1474-4422(14)70251-0 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Matsuoka H, Iwase S, Miyaji T et al (2019) Additive duloxetine for cancer-related neuropathic pain nonresponsive or intolerant to opioid-pregabalin therapy: a randomized controlled trial (JORTC-PAL08). J Pain Symptom Manage.  https://doi.org/10.1016/j.jpainsymman.2019.06.020 CrossRefGoogle Scholar
  3. 3.
    Maruo T, Nakae A, Maeda L, Shi K, Takahashi K, Morris S, Hosomi K, Kanatani H, Matsuzaki T, Saitoh Y (2014) Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain. Pain Med 15:1930–1937.  https://doi.org/10.1111/pme.12468 CrossRefPubMedGoogle Scholar
  4. 4.
    Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370CrossRefGoogle Scholar
  5. 5.
    Catastrophizing Quartana PJ, Campbell CM, Edwards RR (2009) Pain catastrophizing: a critical review. Expert Rev Neurother 9:745–758.  https://doi.org/10.1586/ern.09.34 CrossRefPubMedGoogle Scholar
  6. 6.
    Bishop SR, Warr D (2003) Coping, catastrophizing and chronic pain in breast cancer. J Behav Med. 26:265–281CrossRefGoogle Scholar
  7. 7.
    Utne I, Miaskowski C, Bjordal K, Paul SM, Jakobsen G, Rustøen T (2009) Differences in the use of pain coping strategies between oncology in patients with mild vs. moderate to severe pain. J Pain Symptom Manage 38:717–726.  https://doi.org/10.1016/j.jpainsymman.2009.03.005 CrossRefPubMedGoogle Scholar
  8. 8.
    Matsuoka H, Ishiki H, Iwase S, Koyama A, Kawaguchi T, Kizawa Y, Morita T, Matsuda Y, Miyaji T, Ariyoshi K, Yamaguchi T (2017) Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study. BMJ Open 7:e017280.  https://doi.org/10.1136/bmjopen-2017-017280 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Treede RD, Jensen TS, Campbell JN et al (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70:1630–1635.  https://doi.org/10.1111/j.1526-4637.2009.00774.x CrossRefPubMedGoogle Scholar
  10. 10.
    Atkinson TM, Mendoza TR, Sit L, Passik S, Scher HI, Cleeland C, Basch E (2010) The brief pain inventory and its “pain at its worst in the last 24 hours” item: clinical trial endpoint considerations. Pain Med 11:337–346.  https://doi.org/10.1111/j.1526-4637.2009.00774.x CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kugaya A, Akechi T, Okuyama T, Okamura H, Uchitomi Y (1998) (1998) Screening for psychological distress in Japanese cancer patients. Jpn J Clin Oncol 28:333–338CrossRefGoogle Scholar
  12. 12.
    Daut RL, Cleeland CS, Flanery RC (1983) Development of the Wisconsin brief pain questionnaire to assess pain in cancer and other diseases. Pain 17:197–210CrossRefGoogle Scholar
  13. 13.
    Cleeland CS, Ryan KM (1994) Pain assessment: global use of the brief pain inventory. Ann Acad Med Singapore. 23:129–138PubMedGoogle Scholar
  14. 14.
    Dworkin RH, Turk DC, Revicki DA et al (2009) Development and initial validation of an expanded and revised version of the short-form McGill pain questionnaire (SF-MPQ-2). Pain 144:35–42CrossRefGoogle Scholar
  15. 15.
    Uki J, Mendoza T, Cleeland CS, Nakamura Y, Takeda F (1998) A brief cancer pain assessment tool in Japanese: the utility of the Japanese brief pain inventory--BPI-J. J Pain Symptom Manage 16:364–373CrossRefGoogle Scholar
  16. 16.
    Utne I, Miaskowski C, Bjordal K et al (2009) Differences in the use of pain coping strategies between oncology inpatients with mild vs. moderate to severe pain. J Pain Symptom Manage 38:717–726.  https://doi.org/10.1016/j.jpainsymman CrossRefPubMedGoogle Scholar
  17. 17.
    Matsuoka H, Sakano Y (2007) Assessment of cognitive aspect of pain: development, reliability, and validation of Japanese version of pain catastrophizing scale. Jpn J Psychosoma Med 47:95–102Google Scholar
  18. 18.
    Lee PH (2014) Should we adjust for a confounder if empirical and theoretical criteria yield contradictory results? A simulation study. Sci Rep 15(4):6085.  https://doi.org/10.1038/srep06085 CrossRefGoogle Scholar
  19. 19.
    Martin LA, Hagen NA (1997) Neuropathic pain in cancer patients: mechanisms, syndromes, and clinical controversies. J Pain Symptom Manage 14:99–117CrossRefGoogle Scholar
  20. 20.
    Swerdlow M (1980) The treatment of "shooting" pain. Postgrad Med J 56:159–161CrossRefGoogle Scholar
  21. 21.
    Geber C, Breimhorst M, Burbach B, Egenolf C, Baier B, Fechir M, Koerber J, Treede RD, Vogt T, Birklein F (2013) Pain in chemotherapy-induced neuropathy--more than neuropathic? Pain 154:2877–2887.  https://doi.org/10.1016/j.pain.2013.08.028 CrossRefPubMedGoogle Scholar
  22. 22.
    Caraceni A, Portenoy RK (1999) An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. Pain 82:263–274Google Scholar
  23. 23.
    Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y (2012) Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain 153:1193–1198.  https://doi.org/10.1016/j.pain.2012.02.021 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hiromichi Matsuoka
    • 1
    • 2
    • 3
    Email author
  • Satoru Iwase
    • 4
  • Tempei Miyaji
    • 5
  • Takashi Kawaguchi
    • 6
  • Keisuke Ariyoshi
    • 7
  • Shunsuke Oyamada
    • 7
  • Eriko Satomi
    • 8
  • Hiroto Ishiki
    • 8
  • Hideaki Hasuo
    • 9
  • Hiroko Sakuma
    • 9
  • Akihiro Tokoro
    • 10
  • Yoshinobu Matsuda
    • 10
  • Kazuki Tahara
    • 11
  • Hiroyuki Otani
    • 12
  • Yoichi Ohtake
    • 13
  • Hiroaki Tsukuura
    • 14
  • Yoshihisa Matsumoto
    • 15
  • Yoshikazu Hasegawa
    • 16
  • Yuki Kataoka
    • 17
  • Masatomo Otsuka
    • 18
  • Kiyohiro Sakai
    • 1
    • 2
  • Miki Nakura
    • 1
  • Tatsuya Morita
    • 19
  • Takuhiro Yamaguchi
    • 20
  • Atsuko Koyama
    • 1
    • 2
  1. 1.Department of Psychosomatic MedicineKindai University Faculty of MedicineOsakaJapan
  2. 2.Palliative Care CenterKindai University Faculty of MedicineOsakaJapan
  3. 3.Faculty of HealthUniversity of Technology SydneySydneyAustralia
  4. 4.Department of Palliative MedicineUniversity of Saitama Medical UniversitySaitamaJapan
  5. 5.Department of Clinical Trial Data Management, Graduate School of MedicineThe University of TokyoTokyoJapan
  6. 6.Department of Practical PharmacyTokyo University of Pharmacy and Life SciencesTokyoJapan
  7. 7.Japanese Organization for Research and Treatment of Cancer (JORTC)JORTC Data CenterTokyoJapan
  8. 8.Department of Palliative MedicineNational Cancer Center HospitalTokyoJapan
  9. 9.Department of Psychosomatic Internal MedicineKansai Medical UniversityOsakaJapan
  10. 10.Department of Psychosomatic Internal MedicineNational Hospital Organization Kinki-Chuo Chest Medical CenterSakaiJapan
  11. 11.Yamanobe General Hospital Internal medicineNaraJapan
  12. 12.Department of Palliative MedicineNational Kyushu Cancer CenterFukuokaJapan
  13. 13.Itami Seifu Hospital Internal medicineHyogoJapan
  14. 14.Nagoya University HospitalAichiJapan
  15. 15.Department of Palliative MedicineNational Cancer Center EastKashiwaJapan
  16. 16.Department of Medical OncologyIzumi City General HospitalIzumiJapan
  17. 17.Department of Respiratory MedicineHyogo Prefectural Amagasaki General Medical CenterHyogoJapan
  18. 18.Department of Palliative MedicineKindai University Nara HospitalNaraJapan
  19. 19.Palliative and Supportive Care DivisionSeirei Mikatahara General HospitalHamamatsuJapan
  20. 20.Division of BiostatisticsTohoku University Graduate School of MedicineSendaiJapan

Personalised recommendations