Comparative Effectiveness and Tolerability of Topical Capsaicin Versus Pregabalin in Chemotherapy-Induced Peripheral Neuropathy: A Prospective Observational Study

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating complication of neurotoxic chemotherapy, significantly affecting quality of life and treatment adherence in cancer patients. Pharmacological management remains challenging, with limited efficacy and tolerability of commonly used systemic agents. Objective: To compare the effectiveness and safety of topical capsaicin and oral pregabalin in patients with CIPN receiving neurotoxic chemotherapy. Methodology: This prospective, observational comparative study was conducted from January to December 2023 at the Clinical Oncology Department of Swat Institute of Nuclear Medicine Oncology and Radiotherapy, Pakistan. A total of 117 patients who developed new-onset CIPN during or after chemotherapy were included. Patients received either topical capsaicin 0.075% (Group-A, n = 77) or oral pregabalin (Group-B, n = 40). Symptom improvement was assessed at two and six weeks. Adverse events, treatment compliance, and discontinuation rates were also recorded. Statistical analysis included chi-square tests, independent t-tests, and logistic regression adjusted for chemotherapy regimen. Results: Both groups demonstrated symptom improvement; however, response rates were significantly higher in the capsaicin group at both two weeks (85.7% vs. 32.5%, p = 0.005) and six weeks (93.5% vs. 32.5%, p = 0.001). Logistic regression confirmed superior efficacy of capsaicin [OR 6.2; 95% CI 2.8–13.5]. No systemic adverse events were reported with capsaicin, whereas pregabalin was associated with dizziness, edema, and sleepiness, leading to high treatment discontinuation. Conclusion: Topical capsaicin demonstrated superior efficacy and better tolerability compared with pregabalin in the management of CIPN. These findings suggest that topical capsaicin may represent a safer and more effective alternative for symptomatic relief in patients receiving neurotoxic chemotherapy. Keywords: Antineoplastic Agents, Capsaicin, Neuralgia, Peripheral Nervous System Diseases, Pregabalin.