Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Multi-centre, Randomised, Double-blind, Placebo-controlled Trial of Additive Duloxetine for Cancer-related Neuropathic Pain Refractory to Opioids and Gabapentinoids (#339)

Hiromichi Matsuoka 1 2 , Satoru Iwase 3 , Tempei Miyaji 4 , Takashi Kawaguchi 5 , Keisuke Ariyoshi 6 , Shunsuke Oyamada 6 , Eriko Satomi 7 , Hiroto Ishiki 7 , Hideaki Hasuo 8 , Hiroko Sakuma 8 , Akihiro Tokoro 9 , Toshiaki Shinomiya 10 , Hiroyuki Otani 11 , Yoichi Otake 12 , Tsukuura Hiroaki 13 , Yoshihisa Matsumoto 14 , Yoshikazu Hasegawa 15 , Yuki Kataoka 16 , Masatomo Otsuka 17 , Kiyohiro Sakai 2 , Yoshinobu Matsuda 9 , Tatsuya Morita 18 , Atsuko Koyama 2 , Takuhiro Yamaguchi 19
  1. University of Technology Sydney, Ultimo, NSW, Australia
  2. Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
  3. Department of Pallaitive Medicine, Saitama Medical University Hospital, Saitama , Saitama, Japan
  4. University of Tokyo, Tokyo, Japan
  5. Tokyo University of Pharmacy and Life Sciences, Tokyo,, Tokyo, Japan
  6. JORTC Data Center, Tokyo, Japan
  7. National Cancer Center Hospital, Tokyo, Japan
  8. Kansai Medical University, Hirakata, Osaka, Japan
  9. National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan
  10. Nara Medical University, Kashihara, Nara, Japan
  11. National Kyushu Cancer Center, Fukuoka, Japan
  12. Sakai City Medical Center, Sakai, Osaka, Japan
  13. Nagoya University Hospital, Nagoya, Aichi, Japan
  14. National Cancer Center East, Kashiwa, Chiba, Japan
  15. Izumi City General Hospital, Izumi, Osaka, Japan
  16. Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan
  17. Kindai University Nara Hospital, Nara, Japan
  18. Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
  19. Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Aims

We investigated the efficacy of duloxetine administration for cancer-related neuropathic pain refractory to opioid-gabapentinoid combination therapy.

Methods

This was a multicenter, randomized, double-blind, placebo-controlled trial (the DIRECT study; registration number UMIN000017647). Patients with any cancer-related neuropathic pain, currently taking opioids, who were nonresponsive or intolerant to gabapentinoids were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine or placebo 20 mg–40 mg for 10 days. The primary endpoint was average pain intensity (Brief Pain Inventory [BPI] item 5) at day 10 (BPI d10).

Results

Seventy patients were enrolled at 12 sites. BPId0 (before treatment) was 5.6 for group D (duloxetine) and 5.7 for group P (placebo). Mean BPId10 scores for the complete case (CC) analysis were 4.03 for group D (90% confidence interval [CI]: 3.33, 4.74) and 4.88 for group P (90% CI: 4.37, 5.38) (P = .053). Mean BPId10 values for the baseline observation carried forward (BOCF) analysis were 4.06 for group D (90% CI: 3.37, 4.74) and 4.91 for group P (90% CI: 4.41, 5.41) (P = .048). Point estimates of differences in average values between the two groups were -0.84 (90% CI: -1.71, 0.02) for the CC analysis and -0.85 (90% CI: -1.69, -0.01) for the BOCF analysis. Between days 0 and 10, 44.1% of patients in group D and 18.2% of patients in group P reported pain improvement ≥ 30% (P = .022); for that same timeframe, 32.4% of patients in group D and 3.0% of patients in group P reported pain improvement ≥ 50% (P = .002).

Conclusions

Duloxetine is a clinically effective additive to opioids for alleviating cancer-related neuropathic pain.