Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08)

• Published in: Journal of pain and symptom management Vol. 58; no. 4; pp. 645 - 653
• Main Authors: Matsuoka, Hiromichi, Iwase, Satoru, Miyaji, Tempei, Kawaguchi, Takashi, Ariyoshi, Keisuke, Oyamada, Shunsuke, Satomi, Eriko, Ishiki, Hiroto, Hasuo, Hideaki, Sakuma, Hiroko, Tokoro, Akihiro, Shinomiya, Toshiaki, Otani, Hiroyuki, Ohtake, Yoichi, Tsukuura, Hiroaki, Matsumoto, Yoshihisa, Hasegawa, Yoshikazu, Kataoka, Yuki, Otsuka, Masatomo, Sakai, Kiyohiro, Matsuda, Yoshinobu, Morita, Tatsuya, Koyama, Atsuko, Yamaguchi, Takuhiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2019; Elsevier Limited
• Subjects: Cancer; cancer-related neuropathic pain; Chemotherapy; Clinical research; Clinical trials; Combination therapy; duloxetine; Efficacy; Evidence-based medicine; Narcotics; Nervous system; opioid-pregabalin therapy; Opioids; Pain; Pain management; Palliative care; Patients; randomized controlled trial; opioid-pregabalin therapy; duloxetine; cancer-related neuropathic pain; Pain; randomized controlled trial
• ISSN: 0885-3924; 1873-6513
• DOI: 10.1016/j.jpainsymman.2019.06.020

Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.
We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.
A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]–Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.
Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002).
Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine.