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The Clinical and Basic Study of Oxaliplatin-Related Neurotoxicity

Author: LiMingYing
Tutor: SongSanTai；XuJianMing
School: PLA Military Academy of Medical Sciences
Course: Oncology
Keywords: Oxaliplatin Neurotoxicity Calcium and magnesium mixture Sodium channel
CLC: R96
Type: Master's thesis
Year: 2007
Downloads: 130
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Abstract

Purpose: Oxaliplatin is a new generation platinum derivative, has played a good role in the clinical treatment of malignant tumors. The dose-limiting toxicity of oxaliplatin peripheral nerve toxicity, neurotoxicity caused by oxaliplatin cause significant discomfort affecting the patient's quality of life, and may be associated with significant dysfunction. Different hypothesis for the mechanism of oxaliplatin neurotoxicity, research and try different control methods, studies have shown that the combination of calcium and magnesium mixture on the prevention and treatment of neurotoxicity oxaliplatin treatment process. In this study, a preliminary discussion of the mechanism of calcium and magnesium mixture prevention and treatment of oxaliplatin neurotoxicity clinical effects as well as oxaliplatin neurotoxicity. Methods: This study included randomized controlled clinical studies and experimental studies of two parts, (1) Select the period from June 2004 to April 2007 at the Military Medical Academy Hospital gastrointestinal medical oncologist oxaliplatin tumor patients randomized in study the clinical application of calcium and magnesium mixture Prevention of oxaliplatin neurotoxicity effects; (2) patch clamp experiments to study the extracellular and intracellular administration of oxaliplatin rat spinal dorsal root ganglion cell membrane sodium channel current . Results: The clinical use of oxaliplatin led to produce nearly 90% of patients with different severity of symptoms of neurotoxicity, and the emergence of neurotoxicity severity of a dose-effect relationship. Neurotoxic symptoms cases all concentrated in the low cumulative dose group; Ⅱ degree and above neurotoxic symptoms cases all concentrated in the middle and high cumulative dose group, significant differences (P <0.001); mixture group plus calcium and magnesium patients, whether it is mild, acute neurological symptoms (numbness or hypoesthesia oral throat paresthesia), prolonged or numbness, fine motor disorder II - III degree of toxicity symptoms, incidence compared with the control group were significantly lower (P <0.05); cases of neurological symptoms can not be tolerated in the control group, after the immediate addition of calcium and magnesium mixture, the symptoms can continue after chemotherapy treatment. Calcium and magnesium mixture significantly improved the quality of life for patients with neurological symptoms in the treatment process. Oxaliplatin administration inhibit intracellular sodium ion channel currents in rat dorsal root neurons in cell voltage gate control large, three types of cells in the administration of 5 minutes, 10 minutes and 15 minutes, the amplitude of the sodium ion current administration former compared have significantly lower (p <0.05), and at different time points after administration of small cell Na + current amplitude inhibition rate was significantly greater than the same period in the large cells and cells suppress inhibition was significantly higher than that of small cells large cells and in cells (p <0.05). Conclusion: Oxaliplatin can lead to the generation of neurotoxic symptoms, neurotoxicity incidence and severity of dose-effect relationship exists; the calcium magnesium mixture Prevention neurotoxic effects of oxaliplatin obvious, its application can significantly improve the neurological symptoms in the treatment process the patient's quality of life; administered oxaliplatin cells inhibited rat dorsal root neurons voltage-gated sodium channel current, and of small cell sodium channel current inhibition was significantly higher than that of large cells and in cells.

The Clinical and Basic Study of Oxaliplatin-Related Neurotoxicity

Abstract

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