Role of Duloxetine in the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Patients Receiving Paclitaxel

Abstract

Paclitaxel-induced peripheral neuropathy (PIPN) is a common, dose-limiting toxicity that impairs quality of life and often necessitates chemotherapy dose reduction or discontinuation. To date, no effective prophylactic agent has been established. Duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI) approved for diabetic neuropathy and chronic pain syndromes, has demonstrated efficacy in treating established chemotherapy-induced peripheral neuropathy (CIPN). This study evaluated the preventive efficacy of duloxetine in reducing the incidence and severity of PIPN.

The aim is to study the effect of duloxetine in the prevention of CIPN in patients receiving paclitaxel (NCI CTCAEv5.0) and to compare dose modification of paclitaxel due to peripheral neuropathy in each arm.

This prospective, randomized, non-blinded, interventional study was conducted in the Department of Medical Oncology, Government Stanley Medical College and Hospital, Chennai, over 12 months. Sixty chemotherapy-naïve patients receiving paclitaxel in adjuvant, neoadjuvant, or palliative settings were randomized equally into two arms. The intervention arm received duloxetine 30 mg once daily for 1 week, followed by 60 mg once daily for 3 months, starting from the first chemotherapy cycle. The control arm received standard paclitaxel therapy without duloxetine (no additional drug as placebo given). Peripheral neuropathy was assessed clinically using NCI-CTCAE version 5.0 and electrophysiologically with nerve conduction studies (NCS). Secondary endpoints included paclitaxel dose modification, treatment interruption, and requirement for additional analgesic intervention.

Peripheral neuropathy occurred in 33% of patients in the duloxetine arm compared to 70% in the control arm (p = 0.004). Dose modification (13.3 vs. 66.7%; p <0.001), treatment interruption (10 vs. 40%; p = 0.007), and analgesic requirement (13.3 vs. 56.7%; p = 0.001) were significantly reduced. NCS confirmed superior nerve preservation with duloxetine (p <0.001).

Duloxetine prophylaxis significantly reduced both the incidence and severity of PIPN and improved chemotherapy tolerance. Its favorable safety profile, oral administration, and affordability make it a promising neuroprotective adjunct in paclitaxel-based regimens. Larger multicentric studies are warranted to validate these findings for clinical adoption.