Association of renin–angiotensin–aldosterone system inhibitors with paclitaxel-induced peripheral neuropathy

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients’ quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin–angiotensin–aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN). Methods: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine–Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding. Results: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into the RAAS inhibitor group (n=1,320) and non-RAAS inhibitor group (n=4,566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in the RAAS inhibitor group than in the non-RAAS inhibitor group (sub-distribution hazard ratio, 0.871; 95% confidence interval, 0.789–0.961). The result was consistent in various sensitivity analyses and important subgroup analyses. Conclusions: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer.