In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: cyclophosphamide and BCNU.
In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: cyclophosphamide and BCNU.
复制标题
抗癌药物与米索硝唑或甲硝唑的体内相互作用：环磷酰胺和 BCNU。
作者：
I. Tannock
在环磷酰胺（CY）治疗中加入米索硝唑（MISO）或甲硝唑（METRO）增加了2个实验性肿瘤再生的延迟。在大小肿瘤中都观察到这种效果，MISO剂量对杀死缺氧细胞无效，并且需要与CY一起或在CY之前给予。接受联合治疗的小鼠比单独接受CY的小鼠体重减轻和骨髓抑制更多，治疗指数更低。当MISO与BCNU联合治疗KHT肉瘤时，生长延迟明显增加。这种效应在小肿瘤和大肿瘤中观察到，需要同时给药，也导致宿主毒性增加。联合治疗没有治疗优势。在体外暴露于单独接受CY或BCNU的小鼠血清后，评估有氧或缺氧中国仓鼠卵巢（CHO）细胞的存活。单用MISO或联合治疗。这些实验结果表明：(1)MISO延缓了CY活性代谢物的排泄或分解，(2)在不杀死缺氧细胞的剂量下，它可能选择性地使缺氧细胞（而不是有氧细胞）对BCNU的作用“敏感”。BCNU和MISO之间存在其他未确定的相互作用，这可以从对（需氧）正常组织的毒性增加中推断出来。接受BCNU或环磷酰胺治疗的患者应谨慎使用米索硝唑或甲硝唑。
The addition of misonidazole (MISO) or metronidazole (METRO) to treatment with cyclophosphamide (CY) increased delay to regrowth of 2 experimental tumours. The effect was observed for large an small tumours, was present for doses of MISO that are ineffective for killing hypoxic cells, and required that it be given with, or shortly before CY. Mice receiving combined treatment had more weight loss and myelosuppression than those receiving CY alone, and the Therapeutic Index was lower. MISO caused a marked increase in growth delay when combined with BCNU to treat the KHT sarcoma. This effect was observed for small and large tumours, required simultaneous administration of drugs, and also led to increased host toxicity. There was no therapeutic advantage from combined treatment. Survival of aerobic or anoxic Chinese hamster ovary (CHO) cells was assessed after exposure in vitro to serum from mice that had received CY or BCNU alone. MISO alone, or combined treatment. Results of these experiments suggest that (1) MISO delays the excretion or breakdown of active metabolites of CY, and (2) at a dose that does not kill hypoxic cells, it may selectively "sensitize" hypoxic cells (but not aerobic cells) to the action of BCNU. The presence of other undetermined interactions of BCNU and MISO is inferred from the increased toxicity to (aerobic) normal tissue. Misonidazole or metronidazole should be used with caution in patients who are receiving BCNU or cyclophosphamide.