乙基去羟基 sparsomycin 与顺铂联合的临床前抗肿瘤活性

Preclinical antitumor activity of ethyldeshydroxysparsomycin in combination with cisplatin.

作者信息

Hofs H P, Wagener D J, De Valk-Bakker V, Van Rennes H, De Vos D, Doesburg W H, Ottenheijm H C, De Grip W J

机构信息

Department of Internal Medicine, Nijmegen University Hospital, The Netherlands.

出版信息

Invest New Drugs. 1995;13(1):23-32. doi: 10.1007/BF02614216.

DOI:10.1007/BF02614216

PMID:7499104

Abstract

The efficacy of cisplatin (CDDP) in combination with the protein synthesis inhibitor ethyldeshydroxysparsomycin (EDSM) has been tested in two tumor models at various schedules. Mice with L1210 leukemia or B16 melanoma were treated with CDDP alone or in combination with EDSM. Against L1210 leukemia, which is sensitive to CDDP, combinations elicited increases in life-span for all treatment schedules compared to those achieved with the corresponding dose of CDDP. Moreover, the combination of EDSM with this platinum compound yielded a cure rate > 80%, compared to < 35% for single CDDP treatment. Although the B16 melanoma is rather resistant to both CDDP and EDSM, combinations of these agents against B16 melanoma showed schedule dependent efficacy and in certain schedules significant therapeutic advantage over individual drug treatment, but cures were not observed. Our results suggest that EDSM has significant synergistic capabilities in both animal tumor models, but strong therapeutic enhancement of cisplatin efficacy is only seen when the tumor is sensitive to CDDP.

摘要

顺铂（CDDP）与蛋白质合成抑制剂乙基去羟基 sparsomycin（EDSM）联合使用的疗效已在两种肿瘤模型中按照不同方案进行了测试。患有 L1210 白血病或 B16 黑色素瘤的小鼠接受了单独的 CDDP 治疗或与 EDSM 联合治疗。对于对 CDDP 敏感的 L1210 白血病，与相应剂量的 CDDP 相比，所有治疗方案的联合用药均使生存期延长。此外，EDSM 与这种铂类化合物联合使用的治愈率>80%，而单独使用 CDDP 治疗的治愈率<35%。尽管 B16 黑色素瘤对 CDDP 和 EDSM 均具有相当的抗性，但这些药物联合用于治疗 B16 黑色素瘤显示出方案依赖性疗效，并且在某些方案中相对于单一药物治疗具有显著的治疗优势，但未观察到治愈情况。我们的结果表明，EDSM 在两种动物肿瘤模型中均具有显著的协同能力，但仅当肿瘤对 CDDP 敏感时，才能看到顺铂疗效的强烈治疗增强作用。