Ohkawa K, Tsukada Y, Dohzono H, Koike K, Terashima Y
Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Br J Cancer. 1988 Jul;58(1):38-41. doi: 10.1038/bjc.1988.157.
The therapeutic antitumour activity and host toxicity of cis-platin (CDDP), which was administered with selenium (sodium selenite) was studied on the growth of a human yolk sac tumour grown in nude mice. Treatment consisted of CDDP single agent chemotherapy (3 weeks) or preliminary PVB combination chemotherapy (CDDP + vinblastine + bleomycin, 2 weeks). Selenium was co-administered from day 1 to 5 with each therapeutic regimen. The administration of CDDP alone caused significant reduction in tumour burden but at higher doses there was significant host toxicity. The co-administration of selenium together with CDDP (CDDP: selenium, molar ratio = 3.5:1) did not affect the anti-tumour activity of CDDP but it did cause a decrease of parameters of host toxicity including lethality, increasing the 50% lethal dose (LD50) from 9.3 mg kg-1 to 17.5 mg kg-1. The parameters of host toxicity which were altered by selenium co-administration were nephrotoxicity, myeloid suppression and weight loss. Our study suggested that selenium co-administration allows higher doses of CDDP with reduction of apparent toxicity, resulting in a higher therapeutic index and possibly indicating a potential increase in the utilization of CDDP in clinical cancer chemotherapy.
研究了顺铂（CDDP）与硒（亚硒酸钠）联合给药对裸鼠体内人卵黄囊瘤生长的治疗抗肿瘤活性和宿主毒性。治疗方案包括CDDP单药化疗（3周）或初步的PVB联合化疗（CDDP + 长春碱 + 博来霉素，2周）。在每个治疗方案中，从第1天到第5天同时给予硒。单独给予CDDP可显著降低肿瘤负荷，但在较高剂量时会出现明显的宿主毒性。硒与CDDP联合给药（CDDP：硒，摩尔比 = 3.5：1）不影响CDDP的抗肿瘤活性，但确实导致宿主毒性参数降低，包括致死率，使50%致死剂量（LD50）从9.3 mg/kg增加到17.5 mg/kg。因联合给予硒而改变的宿主毒性参数包括肾毒性、骨髓抑制和体重减轻。我们的研究表明，联合给予硒可允许使用更高剂量的CDDP，同时降低明显的毒性，从而提高治疗指数，并可能表明在临床癌症化疗中CDDP的利用率有潜在提高。
