Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies

BackgroundThe current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC).MethodsThis is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients.ResultsA total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P=0.501; P=0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P=0.598; P=0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P=0.600), laryngeal dysthesia (P=0.707), jaw pain (P=0.743) or muscle pain (P=0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P=0.107), highest grade of paresthesia (P=0.498) or rates of recovery from paresthesia (P=0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P=0.024).ConclusionDM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.