Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy

OBJECTIVE: To evaluate the role of glutamine in the reduction of peripheral neuropathy associated with neurotoxic chemotherapy. DATA SOURCES: Relevant literature was accessed through PubMed (1990-May 2008), using the search terms glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkaloids. References in the identified articles were also reviewed for pertinent information. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the role of oral glutamine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) were included. Studies regarding the role of glutamine in the reduction of other radiation- and chemotherapy-related toxicities, such as mucositis, cardiotoxicity, diarrhea, and cachexia, were excluded. DATA SYNTHESIS: CIPN is a significant adverse effect associated with neurotoxic chemotherapy, particularly with taxanes, platinum compounds, and vinca alkaloids. There is no standard therapy for the treatment of this dose-limiting reaction. Glutamine is a nonessential amino acid that is thought to have a neuroprotective role, possibly due to the upregulation of nerve growth factor. Two studies revealed that oral glutamine was effective in reducing peripheral neuropathy associated with high-dose paclitaxel, as evidenced by a reduction in numbness, dysesthesias, and motor weakness, as well as a smaller loss of vibratory sensation. Another study found that glutamine effectively reduced peripheral neuropathy in patients with colorectal cancer being treated with oxaliplatin, thereby decreasing the need for an oxaliplatin dose reduction. However, data are limited by small sample sizes in these studies and the lack of placebo-controlled, randomized clinical trials. CONCLUSIONS: Larger, well-designed, placebo-controlled trials assessing both safety and efficacy of oral glutamine are warranted before this agent can be definitively recommended for the prevention of CIPN in patients treated with high-dose paclitaxel or oxaliplatin.