NEUROPROTECTIVE EFFECT OF REDUCED GLUTATHIONE ON CISPLATIN-BASED CHEMOTHERAPY IN ADVANCED GASTRIC-CANCER - A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL
NEUROPROTECTIVE EFFECT OF REDUCED GLUTATHIONE ON CISPLATIN-BASED CHEMOTHERAPY IN ADVANCED GASTRIC-CANCER - A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL
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DOI：
10.1200/jco.1995.13.1.26
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发表时间：
1995-01-01
影响因子：
45.3
通讯作者：
CATALANO, G
中科院分区：
文献类型：
--
作者：
CASCINU, S;CORDELLA, L;CATALANO, G
目的：我们进行了一项随机双盲安慰剂对照试验，以评估谷胱甘肽（GSH）在预防顺铂（CDDP）诱导的神经毒性中的疗效。患者和方法：本研究纳入了50例接受每周一次cddp治疗的晚期胃癌患者。在随机接受谷胱甘肽治疗的患者中，在给药前15分钟，在100ml生理盐水溶液中给予1.5 g/m(2)的谷胱甘肽，在第2天至第5天肌肉注射600 mg的谷胱甘肽。给予安慰剂随机分组的患者生理盐水。在基线和治疗9周（CDDP剂量，360 mg/m(2)）和15周（CDDP剂量，600 mg/m(2)）后进行临床神经学评估和电生理检查。结果：在第9周，GSH组没有患者出现临床明显的神经病变，而安慰剂组有16例患者出现。15周后，GSH组24名可评估患者中有4名出现神经毒性，而安慰剂组18名患者中有16名出现神经毒性（P = 0.0001）。为了证实这种神经保护作用，基于正中、尺侧和腓肠感觉神经传导评估的神经生理学调查显示，在安慰剂组中，这些值有统计学意义上的显著降低，但在GSH组中没有，首先考虑到电位振幅。在这项试验中，谷胱甘肽还减少了输血需求（32 v 62次输血）和治疗延迟（55 v 94周）。GSH组的反应率为76%（20%完全缓解），安慰剂组的反应率为52%（12%完全缓解），证实了关于GSH诱导的细胞毒性药物活性缺乏降低的初步报告。结论：本研究证明谷胱甘肽是一种很有前景且有效的预防cdp性神经病变的新药，且不会降低化疗药物的临床活性。
Purpose: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity.Patients and Methods: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m(2) in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m(2)) and 15 (CDDP dose, 600 mg/m(2)) weeks of treatment.Results: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH.Conclusion: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.