Treatment of tumours with the combination of WR-2721 and cis-dichlorodiammineplatinum (II) or cyclophosphamide.
Treatment of tumours with the combination of WR-2721 and cis-dichlorodiammineplatinum (II) or cyclophosphamide.
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DOI：
10.1038/bjc.1980.282
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发表时间：
1980-10
影响因子：
8.8
通讯作者：
Culo, F
中科院分区：
文献类型：
--
作者：
Yuhas, J M;Spellman, J M;Jordan, S W;Pardini, M C;Afzal, S M;Culo, F
在携带3种不同肿瘤的小鼠和大鼠中研究了WR-2721 [S-2（3-氨基丙基氨基）乙基-硫代磷酸]选择性保护宿主免受多剂量顺式二氯二氨铂[cis-Pt]或环磷酰胺[CY]毒性作用的能力。在所有研究条件下均证明了对顺式铂诱导的肾毒性的选择性保护，保护程度与顺式铂剂量的大小呈负相关。例如，在每周2 mg/kg顺式铂给药前30分钟用200 mg/kg WR-2721预处理，可使该细胞毒性剂在肾毒性损伤前的给药时间延长3倍。在这些研究中，没有一项是肿瘤保护。在CY中观察到相同的模式，但由于该药物诱导和观察到的死亡之间的潜伏期较长，因此无法对多次给药研究的骨髓保护程度进行定量。因此，我们的结论是，对于这两种药物，选择性保护肾脏和骨髓不仅保持在多种治疗的条件下，但实际上由于需要更小剂量的细胞毒性药物在这些协议中增强。
The ability of WR-2721 [S-2(3-aminopropylamino)ethyl-phosporothioic acid] to selectively protect the host against the toxic effects of multiple doses of cis-dichlorodiammineplatinum [cis-Pt] or cyclophosphamide [CY] has been studied in mice and rats bearing 3 different tumours. Selective protection against cis-Pt induced nephrotoxicity has been demonstrated under all conditions studied, with the extent of protection being inversely related to the size of the cis-Pt dose. For example, pre-treatment with 200 mg/kg of WR-2721 30 min before each weekly dose of 2 mg/kg of cis-Pt allows the administration of this cytotoxic agent for 3 times longer before nephrotoxic injury. In none of these studies was there tumour protection. The same pattern was observed with CY, but quantitation of the extent of marrow protection was not possible for the multiple treatment studies, due to the longer latent period between induced and observed death with this drug. We conclude, therefore, that for both of these drugs, selective protection of the kidney and marrow is not only maintained under conditions of multiple treatment, but actually enhanced due to the need for smaller doses of cytotoxic agents in these protocols.