N(2)-L-Alanyl-L-Glutamine Dipeptide Preventing Oxaliplatin-Induced Neurotoxicity in Colorectal Cancer Patients

Abstract

Oxaliplatin and infusional fluorouracil/leucovorin or capecitabine ha s 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) enter ed 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.