Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial—JORTC-PAL08 (DIRECT) study
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.
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.
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).
Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.
KeywordsDuloxetine Neuropathic cancer pain Palliative care Randomized controlled trial Secondary analyses
- 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
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.
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
The authors declare that they have no competing interests.
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.
Sasakawa Health Foundation
Nippon Foundation Building 5F,1-2-2 Akasaka,
Minato-ku,Tokyo 107-0052, Japan
Health Labour Sciences Research Grant
5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan
Ministry of Health, Labour and Welfare
1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916, Japan
Minato-ku,Tokyo 107-0052, Japan
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
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