OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.
OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.
Authors: T R Ziegler; K Benfell; R J Smith; L S Young; E Brown; E Ferrari-Baliviera; D K Lowe; D W Wilmore Journal: JPEN J Parenter Enteral Nutr Date: 1990 Jul-Aug Impact factor: 4.016
Authors: V S Klimberg; E Nwokedi; L F Hutchins; A A Pappas; N P Lang; J R Broadwater; R C Read; K C Westbrook Journal: JPEN J Parenter Enteral Nutr Date: 1992 Nov-Dec Impact factor: 4.016
Authors: Noam Yarom; Anura Ariyawardana; Allan Hovan; Andrei Barasch; Virginia Jarvis; Siri Beier Jensen; Yehuda Zadik; Sharon Elad; Joanne Bowen; Rajesh V Lalla Journal: Support Care Cancer Date: 2013-06-14 Impact factor: 3.603
Authors: Krzysztof Piotr Michalak; Agnieszka Maćkowska-Kędziora; Bogusław Sobolewski; Piotr Woźniak Journal: Oxid Med Cell Longev Date: 2015-10-25 Impact factor: 6.543