TITLE:
N(2)-L-Alanyl-L-Glutamine Dipeptide Preventing Oxaliplatin-Induced Neurotoxicity in Colorectal Cancer Patients
AUTHORS:
Adel Gabr, Ahmed A. S. Salem, Haisem Ahmed Samy, Shimaa Tmam, Anwar Mohammed Ali
KEYWORDS:
Colorectal Cancer, Oxaliplatin, FOLFOX-4, Alanylglutamine, Neuropathy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.9,
August
26,
2016
ABSTRACT: Oxaliplatin
and infusional fluorouracil/leucovorin or capecitabine has emerged as important options in the adjuvant and
palliative treatment of colorectal cancer. Severe Oxaliplatin induced
neurotoxicity may require chemotherapy dose reduction or cessation. The
incidence of oxaliplatin-induced neurotoxicity has varied from 12% - 18%.
Several attempts have been proposed to prevent or treat oxaliplatin-induced
neurotoxicity, but treatment of established chronic Oxaliplatin induced
neurotoxicity is limited. Purpose: To
assess the efficacy of parenteral Glutamine dipeptide (N2-L-Alanyl-L-Glutamine
Dipeptide, 20 g·m/100ml,
IV) for preventing of oxaliplatin induced neurotoxicity. Patients and Methods: A pilot study was performed. 120 patients with metastatic colorectal cancer
(mCRC) entered into the study. 60
patients randomly assigned to receive IV glutamine dipeptide (20 g·m IV) day 1-2 with FOLFOX-4 to be repeated every 15 days as a
first line of treatment of metastatic colorectal cancer and 60 patients
assigned to receive only FOLFOX-4 (control group). Neurotoxicity symptoms and
signs were evaluated before each cycle. Results: There were significantly
fewer neurological symptoms in patients receiving glutamine dipeptide than in
those who did not. A decreased percentage of grade 1-2 peripheral neuropathy was observed in the
glutamine dipeptide group after two cycles (8.3% versus 20%; P = 0.04) and 4 cycles (13.3% vs 26.7%; P = 0.02). A significantly lower incidence of grade 3-4 neuropathy was noted in the glutamine dipeptide
group after four and six cycles (6.7% versus 15%, P = 0.02 and 13.3% versus 33.3%. P = 0.04,
respectively). The need for oxaliplatin dose reduction was significantly lower
in the glutamine dipeptide (Dipeptiven) group (10% vs 26.7%; P = 0.02) and
there were no significant differences between two groups in response to
chemotherapy among patient with mCRC (48.3% vs 50%). Conclusion: These data
concluded that IV dipeptide glutamine significantly decreases the incidence and
severity of oxaliplatin induced neurotoxicity of mCRC without any attendant
side effects.