Abstract 49P
Background
Metformin (MTF), antidiabetic drug, has therapeutic potential against metastatic colorectal cancer (mCRC) by impeding tumor growth and suppressing IL-6 signaling pathway. This study investigates the efficacy and safety of MTF as an adjuvant to FOLFOX-6 in newly diagnosed non-diabetic mCRC patients (pts).
Methods
A prospective, randomized, open-label, controlled study enrolled 70 ECOG ≤ 2, non-diabetic, chemotherapy-naïve mCRC Pts. They were randomized (1:1) to receive FOLFOX-6 alone (Control group, CG =35) or MTF 1 gm OD added to FOLFOX-6 (MTF group, MG =35) for 12 cycles. Overall response rate (ORR), 1-yr progression-free survival (PFS), and 1-yr overall survival (OS) were the main study outcomes. Also, health-related quality of life (HRQOL) was evaluated using EORTC qlqc30 & qlqc29 at baseline, after 6 and 12 cycles. Toxicity was assessed using CTCAE V4. Also, serum IL-6 was measured before and after the end of treatment.
Results
In this study, mean age was 57.1 yrs with 54.29% of pts being males. ORR was significantly superior in MG vs CG (48.57% vs 22.86%; P=0.0115). Also, 1-yr PFS (68.57% vs 20%; P=<0.001) and OS (62.86% vs 22.86%; P=0.00095) rates were significantly higher in MG vs CG respectively. Further, in all AEs, MG reported significantly lower incidence and severity vs CG regarding peripheral neuropathy (P=<0.0001), hand-foot syndrome (P=0.0111), arthralgia (P =<0.0001), headache (P=0.0006), oral mucositis (P= 0.0001), confusion (P =0.0408) and tinnitus (P =0.0248). As for HRQOL, MG showed improvement in physical function (P=0.034), emotional function (P=0.045), cognitive function (P=0.025), insomnia (P=0.041), constipation (P=0.035), financial difficulties (P=0.034), body and sexual images with P=0.007 and 0.010 respectively. Although both groups had a statistically significant within-group reduction in IL-6 levels (P=<0.001); the median percent reduction of -74.0 and -76.6 in CG and MG respectively (P=0.3159) was non-significant.
Conclusions
Metformin as adjuvant therapy to FOLFOX 6 in non-diabetic mCRC pts have improved ORR, PFS, OS, and HRQOL. Also, it ameliorated chemotherapy toxicities. However, IL-6 levels were comparable between study groups. Larger studies are needed for validation.
Clinical trial identification
NCT05921942.
Legal entity responsible for the study
Faculty of Medicine - Ain Shams University Ethical Committee.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.