Savarese Diane M F, Savy Gayle, Vahdat Linda, Wischmeyer Paul E, Corey Barbara
Division of Hematology Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Cancer Treat Rev. 2003 Dec;29(6):501-13. doi: 10.1016/s0305-7372(03)00133-6.
Malignancy produces a state of physiologic stress that is characterized by a relative deficiency of glutamine, a condition that is further exacerbated by the effects of cancer treatment. Glutamine deficiency may impact on normal tissue tolerance to antitumor treatment, and may lead to dose reductions and compromised treatment outcome. Providing supplemental glutamine during cancer treatment has the potential to abrogate treatment-related toxicity. We reviewed the available data on the use of glutamine to decrease the incidence and severity of adverse effects due to chemotherapy and/or radiation in cancer patients.
We performed a search of the MEDLINE database during the time period 1980-2003, and reviewed the English language literature of both human and animal studies pertaining to the use of glutamine in subjects with cancer. We also manually searched the bibliographies of published articles for relevant references.
The available evidence suggests that glutamine supplementation may decrease the incidence and/or severity of chemotherapy-associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced neuropathy, hepatic veno-occlusive disease in the setting of high dose chemotherapy and stem cell transplantation, and the cardiotoxicity that accompanies anthracycline use. Oral glutamine supplementation may enhance the therapeutic index by protecting normal tissues from, and sensitizing tumor cells to chemotherapy and radiation-related injury.
The role of glutamine in the prevention of chemotherapy and radiation-induced toxicity is evolving. Glutamine supplementation is inexpensive and it may reduce the incidence of gastrointestinal, neurologic, and possibly cardiac complications of cancer therapy. Further studies, particularly placebo-controlled phase III trials, are needed to define its role in chemotherapy-induced toxicity.
恶性肿瘤会引发一种生理应激状态,其特征为谷氨酰胺相对缺乏,而癌症治疗的影响会进一步加剧这种情况。谷氨酰胺缺乏可能会影响正常组织对抗肿瘤治疗的耐受性,并可能导致剂量减少和治疗效果受损。在癌症治疗期间补充谷氨酰胺有可能消除与治疗相关的毒性。我们回顾了关于使用谷氨酰胺降低癌症患者化疗和/或放疗不良反应发生率和严重程度的现有数据。
我们在1980年至2003年期间检索了MEDLINE数据库,并回顾了有关癌症患者使用谷氨酰胺的人类和动物研究的英文文献。我们还手动检索了已发表文章的参考文献目录以获取相关参考文献。
现有证据表明,补充谷氨酰胺可能会降低化疗相关口腔黏膜炎、伊立替康相关腹泻、紫杉醇引起的神经病变、高剂量化疗和干细胞移植时的肝静脉闭塞性疾病以及蒽环类药物使用时伴随的心脏毒性的发生率和/或严重程度。口服补充谷氨酰胺可能通过保护正常组织免受化疗和放疗相关损伤并使肿瘤细胞对其敏感来提高治疗指数。
谷氨酰胺在预防化疗和放疗引起的毒性方面的作用正在不断演变。补充谷氨酰胺成本低廉,并且可能会降低癌症治疗中胃肠道、神经和可能的心脏并发症的发生率。需要进一步的研究,特别是安慰剂对照的III期试验,来确定其在化疗引起的毒性中的作用。