Randomized control trial to validate mitigation of chemotherapy-induced peripheral neuropathy by limb-cooling apparatus in breast cancer patients receiving paclitaxel (CECILIA).

12002 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event affecting patient quality of life. Limb cooling may help to prevent CIPN, but no phase 3 trials have confirmed its efficacy, and its efficacy and safety remain challenging. This trial determined if temperature-controlled limb cooling could reduce CIPN in patients with breast cancer receiving weekly perioperative paclitaxel (PTX). Methods: This multicenter, double-blind, randomized controlled trial (jRCT2032210115) assigned patients with breast cancer scheduled to receive 12 weekly doses of perioperative PTX (60 min 80 mg/m 2 intravenous infusion) chemotherapy randomly (1:1) to limb-cooling therapy at a constant temperature of 13°C (Experimental arm) or 25°C (Control arm). The primary endpoint was the proportion of patients with Patient Neurotoxicity Questionnaire (PNQ) ≥D in their limbs after PTX treatment or at the time of discontinuation. Secondary endpoints were NCI-PRO-CTCAE™, EORTC QOL-QLQ-C30, and CIPN-20, and adverse events of cooling therapy. We assumed primary endpoints of 37% and 15% in the Control and Experimental arms, respectively. The planned sample size was 150 to detect a difference (Fisher’s exact test, power 80%, 1-sided alpha 2.5%). Results: The study randomized 150 patients (n = 75 each arm). The PTX treatment completion rates (≥80%) were 88.0% (66/75) in the Experimental and 93.3% (70/75) in the Control arm. The proportion of patients with PNQ ≥D by the end of the treatment (primary endpoint) was similar in both arms (13°C vs. 25°C, 33.3% [25/75] vs. 29.3% [22/75], 1-sided p = 0.76). The proportions were higher in the Experimental arm 3 months after the end of PTX and in patients registered from June to September (Table). The proportion of patients with PNQ ≥D was higher in patients with hand epidermal temperature below the mean (21.5°C) at completion of PTX infusion than in the whole population (38.5%, Table). No frostbite or adverse events were reported in either arm. Conclusions: The primary endpoint did not meet and the limb cooling therapy using a stable cooling device resulted in lower proportion of PNQ ≥ D than was assumed for the Control arm irrespective of temperature settings, warranting further studies to determine optimal temperature. Clinical trial information: jRCT2032210115 . Efficacy 13°C cooling(95%CI) 25°C cooling (95%CI) P value PNQ ≥D (primary endpoint) 33.3% (22.9–45.2) 29.3 % (19.4–41.0) 0.76 NCI-PRO-CTCAE 48.0% (95%CI 36.3–59.9) 49.3 % (37.6–61.1) 0.87 EORTC QLQ-CIPN20 (% non-worsening scores) 28.1% (95%CI 17.6–40.8) 8.8 % (3.3–18.2) 0.006 PNQ ≥D 3 months after end of PTX 32.0% (95%CI 21.7–43.8) 16.2 % (8.7–26.6) 0.034 PNQ ≥D in pts registered June–September 58.1% (39.1–75.5) 25.8 % (11.9–4.6) 0.020 PNQ ≥D in pts with hand epidermal temperature <21.5°C 38.5% (23.4–55.4) - -