We investigated the efficacy of duloxetine administration for cancer-related neuropathic pain refractory to opioid-gabapentinoid combination therapy.
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).
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).
Duloxetine is a clinically effective additive to opioids for alleviating cancer-related neuropathic pain.