Effect of Cilostazol on Preventing Paclitaxel-Induced Neuropathy in Patients with Breast Cancer: A Randomized Controlled Trial.

Abstract

Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer. This study is a parallel randomized placebo-controlled trial. Patients (n=69) with breast cancer scheduled to receive paclitaxel 175 mg/m2 biweekly were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead. The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL). The incidence of grade two, and three peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to control group (86.7%) (P < 0.001). The incidence of clinically significant worsening in neuropathy related QoL was higher in control group compared to cilostazol group (P = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (P = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (P = 0.593). Adjunctive use of cilostazol may be considered as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.