Losartan reduces incidence and delays onset of paclitaxel-induced peripheral neuropathy in women with early-stage breast cancer.

BACKGROUND: Paclitaxel-induced peripheral neuropathy (PIPN) is a condition that persists chronically in more than 60% of affected individuals, and currently there are no proven PIPN prophylaxis. Pre-clinical data suggest the angiotensin-II-receptor blocker losartan may attenuate neuro-inflammation and nerve injury. This study was conducted to assess losartan's neuroprotective effect against PIPN in patients with breast cancer. METHODS: In this single-center, open-label, randomized, controlled trial, women with early-stage breast cancer scheduled for weekly paclitaxel (80 mg/mg or 12 doses) were enrolled and randomized 1:1 to losartan 100 mg once daily plus standard care or standard care alone. The primary end point was incidence of grade 2 or higher neuropathy, per National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE v5.0). Secondary end points included time-to-neuropathy (in days), patient quality of life (QoL) assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX), pain intensity using visual-analogue scale (VAS), serum nerve growth factor (NGF) levels, and safety. RESULTS: Between December 2023 and December 2024, 89 Patients Were Randomized (Losartan, n = 45; Control, n = 44). Losartan Significantly Reduced Grade ≥ 2 Neuropathy Incidence (33.3% vs. 86.4%, p < 0.001) and Delayed Its Onset (73.27 vs. 43.75 Days; Hazards Ratio [HR] = 0.2, 95% Confidence Interval [CI]: 0.11-0.35) Compared With Standard Care Alone, Respectively. At 12 Weeks, Patients Treated With Losartan Reported Superior QoL (FACT/GOG-NTX: 31.87 ± 6.43 vs. 15.45 ± 10.04; p < 0.001) and Reduced Pain Scores (Median VAS 3 vs. 8; p < 0.001) Compared With Standard Care Alone, Respectively. NGF Levels Were Comparable and Adverse Events Were Similar Between Groups. CONCLUSIONS: Daily losartan reduced and delayed clinically significant paclitaxel-induced neuropathy while improving patient-reported outcomes, without additional toxicity. These findings support repurposing losartan as a low-cost PIPN prophylactic and justify validation in larger, multicenter trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06135493).