The study aims at investigating the use of anti-oxidant L-carnosine for prevention of acute oxaliplatin neurotoxicity in colorectal cancer pts and to observe L-carnosine effect on Tumor necrosis factor alpha (TNF α) as a neuro-inflammatory cytokine.
This is a pilot study that recruited 60 pts using prospective randomized controlled design. Eligible Pts (non-diabetic) were randomly assigned to two arms. Arm A (30 pts) received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B (30 pts) received FOLFOX-6 regimen and oral L-carnosine 1000 mg daily all along the treatment. All recruited pts were followed for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to NCI-CTC version 4. Pre-treatment and after 3 months TNF α serum levels were collected and tested.
No neuropathy were detected in 35.3% of pts in Arm B compared to only 3.3% in Arm A. Also 50 % of pts in Arm B developed grade I neuropathy compared to 36.7% in Arm A and only 2.9% of Arm B pts developed grade II neuropathy compared to 60 % of arm A pts. Regarding TNF α serum levels, Arm B and Arm A at base line had comparable mean serum levels (0.04ng/ml & 0.03ng/ml) however the percentage reduction of Arm B serum level was higher than Arm A (0.02ng/ml & 0.001ng/ml, respectively p value = 0.0001). No toxicities were observed due to L-carnosine addition.
Arm A and Arm B regarding the neuropathy grade and TNF before/after 3 months of treatment
|Arm A (Control group) N = 30||Arm B (Test group) N = 30||P-value|
|Neuropathy grade 0 1 2 Drop out||1 (3.3%) 11 (36.7%) 18 (60.0%) 0 (0.0%)||12 (35.3%) 17 (50.0%) 1 (2.9%) 4 (11.8%)||0.0002|
|TNF before start of treatment (ng/ml) Mean ± SD Range||0.03 ± 0.01 0.021 – 0.06||0.04 ± 0.01 0.02 – 0.06||0.664|
|TNF after 3 months of treatment (ng/ml) Mean ± SD Range||0.03 ± 0.01 0.016 – 0.044||0.02 ± 0.01 0.01 – 0.04||0.0001|
L-carnosine reduced the incidence of acute oxaliplatin induced neuropathy, delayed the onset of chronic neuropathy and decreased TNF α serum levels without additional toxicities. Further studies are warranted to examine the full potential of L-carnosine in chemotherapy induced neuropathy.
Clinical trial identification
Local registry: CairoUniv 387658
Legal entity responsible for the study
Faculty of Medicine, Ain Shams University
Faculty of Medicine, Ain shams university Misr international university
All authors have declared no conflicts of interest.