Goel R, Cleary S M, Horton C, Kirmani S, Abramson I, Kelly C, Howell S B
Department of Medicine, University of California, San Diego, La Jolla 92093.
J Natl Cancer Inst. 1989 Oct 18;81(20):1552-60. doi: 10.1093/jnci/81.20.1552.
Concurrent administration of sodium thiosulfate (STS) can protect against the nephrotoxic effects of even very-high-dose cisplatin (CDDP) (i.e., 270 mg/m2 given intraperitoneally). The effect of STS on the pharmacology and toxicity of CDDP was investigated in patients receiving at each treatment 90 mg of CDDP/m2 intraperitoneally, with STS given concurrently on alternate cycles by the intravenous route. The patients received a total of 38 courses of therapy, 21 without STS and 17 with STS. STS reduced the total exposure to diethyldithiocarbamate-reactive CDDP for the peritoneal cavity and plasma by 36% and 25%, respectively. When given alone, CDDP caused a statistically significant acute reduction in creatinine clearance levels; this reduction was less evident when STS was given. We conclude that, whereas STS does reduce systemic exposure, the magnitude of this effect was not sufficient to account for the ability of STS to protect against high-dose CDDP.
同时给予硫代硫酸钠（STS）可以预防即使是非常高剂量顺铂（CDDP）（即腹腔内给予270mg/m²）的肾毒性作用。在每次治疗时腹腔内给予90mg CDDP/m²的患者中，研究了STS对CDDP药理学和毒性的影响，在交替周期中通过静脉途径同时给予STS。患者共接受了38个疗程的治疗，21个疗程未使用STS，17个疗程使用了STS。STS使腹腔和血浆中二乙二硫代氨基甲酸盐反应性CDDP的总暴露量分别降低了36%和25%。单独给予CDDP时，肌酐清除率水平出现统计学上显著的急性降低；给予STS时这种降低不太明显。我们得出结论，虽然STS确实降低了全身暴露，但这种作用的程度不足以解释STS预防高剂量CDDP的能力。
