Gandara D R, Wiebe V J, Perez E A, Makuch R W, DeGregorio M W
University of California, Davis.
Crit Rev Oncol Hematol. 1990;10(4):353-65. doi: 10.1016/1040-8428(90)90010-p.
Cisplatin has a steep dose response curve for both antitumor and adverse effects. Therapeutic strategies aimed at reducing toxicity and allowing dose escalation of intravenous cisplatin, such as administration in hypertonic saline and pharmacokinetically based dosing schedules, have been partially successful in reducing nephrotoxicity and bone marrow suppression. However, new dose-limiting toxicities consisting of peripheral neuropathy and ototoxicity have emerged, which continue to restrict potential use of high dose cisplatin therapy. Intraperitoneal administration of high dose cisplatin also offers the potential of markedly increased local drug exposure if systemic toxicity can be avoided. Proposed chemoprotective agents, including sodium thiosulfate, WR2721, and diethyldithiocarbamate (DDTC) are being extensively examined as "rescue agents" for either regional or systemic administration of cisplatin. Although each agent offers unique advantages to be considered in developing successful rescue therapy, many questions remain regarding molecular and pharmacokinetic interactions with cisplatin, appropriate dosing schedules, and effects on antineoplastic activity. We present a review of current investigations of chemoprotectors for prevention of cisplatin-related toxicities.
顺铂的抗肿瘤作用和不良反应均具有陡峭的剂量反应曲线。旨在降低毒性并允许静脉注射顺铂剂量递增的治疗策略，如在高渗盐水中给药以及基于药代动力学的给药方案，在降低肾毒性和骨髓抑制方面已取得部分成功。然而，新出现的剂量限制性毒性包括周围神经病变和耳毒性，这继续限制了高剂量顺铂疗法的潜在应用。如果能够避免全身毒性，腹腔内给予高剂量顺铂也有可能显著增加局部药物暴露。包括硫代硫酸钠、WR2721和二乙基二硫代氨基甲酸盐（DDTC）在内的拟用化学保护剂正在作为顺铂区域或全身给药的“解救剂”进行广泛研究。尽管每种药物在开发成功的解救疗法时都有独特的优势需要考虑，但关于与顺铂的分子和药代动力学相互作用、合适的给药方案以及对抗肿瘤活性的影响仍存在许多问题。我们对目前预防顺铂相关毒性的化学保护剂研究进行了综述。
