Role of glutamine for preventing oxaliplatin induced peripheral neuropathy (GELUPO): results of randomized open-label phase II trial

Abstract

Background: Aimed to evaluate role of oral glutamine replacement for preventing neuropathy in patients with colorectal cancer receiving oxaliplatin. Methods: The patients planned to receive modified FOLFOX6 were blindly 1:1 randomized to glutamine and control group. In both groups, prior to first mFOLFOX6 regimen and after 8 cycles of therapy detailed neurological examination and EMG was performed. Assuming a neuropathy rate was > 30 % and 10 % in control and glutamine and it was estimated a total of 80 patients needed to be randomized to achieve 80% statistical power with a p level of 0.05 and a 10% drop‐out rate. The patients with neuropathy in basal EMG, diabetes, history of neuropathy were excluded. In glutamine group all of the patients received 3x10 gr/day glutamine given before and during chemotherapy until the control EMG. The secondary end point of study was quality of life evaluated by EORTC‐QLQ C3O. Results: In between December 2013 and September 2015, eighty eligible patients were randomized glutamine (n = 40) and control (n = 40) group. In glutamine and control group basal and control EMG was performed in 87.5% (n = 35) and %80 (n = 32) of the patients, respectively. In between glutamine and control group after 8 cycles of therapy motor axonal and demyelinating neuropathy was detected in 8.5 % (n = 3) vs 18.7 % (n = 6) and 14.2 % (n = 5) vs 15.6 %(n = 5) of the patients and difference was not significant. In between glutamine and control group sensory axonal and demyelinating neuropathy was determined in 14.2 % (n = 5) vs 15.6 % (n = 5) and 17.1 % (n = 6) vs 18.7 % (n = 6) of patients, respectively (p = 1 and p = 0.8). Following the 8 cycles of therapy in control EMG there was no difference in between upper extremity and lower extremity distal latency, compound muscle action potential, motor nerve conduction velocity, F latency, compound nerve action potential and sensory nerve conduction velocity. The hematological and non‐hematological toxicities were similar in between two groups. Basal and control median EORTC‐QLQ scores were not different in between two groups (p = 0.46). Conclusions: In final analysis of the current open label randomized phase II trial, oral glutamine replacement therapy was ineffective to prevent oxaliplatin induced neuropathy.