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
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The 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).
This 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.
A 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).
DM 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.
KeywordsFOLFOX Colon cancer Diabetes mellitus Neuropathy
There is no funding for this study.
Compliance with ethical standards
Conflict of interest
No conflicts of interest.
All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all participants included in the study.
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