Kohno N, Ohnuma T, Biller H F, Holland J F
Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029.
Arch Otolaryngol Head Neck Surg. 1988 Feb;114(2):157-61. doi: 10.1001/archotol.1988.01860140055021.
We compared the efficacy of cisplatin plus fluorouracil vs cisplatin plus cytarabine against HEp-2 head and neck carcinoma cells in monolayer and multicellular tumor spheroid (MTS) systems. Increases in exposure time to cisplatin and fluorouracil from one to 24 hours resulted in approximately tenfold and 1000-fold increases, respectively, in cell lethality for both monolayer and MTS cells. Dose-response curves for cisplatin or fluorouracil on MTS cells closely followed those from monolayer cells, indicating good drug penetration into the MTS core. In contrast, dose-response curves on MTS cells after 24-hour exposure to cisplatin and cytarabine showed progressively lesser efficacy at higher drug concentrations. For monolayer cells, cisplatin plus fluorouracil and cisplatin plus cytarabine were both synergistic, the latter combination more synergistic than the former. For MTS cells, both combinations again showed synergistic interaction at moderate to high effect levels. Heightened synergistic interaction was demonstrated especially with the cisplatin plus cytarabine combination. Thus, the cisplatin plus cytarabine combination was always more synergistic than cisplatin plus fluorouracil. These data may serve as a basis for additional clinical trials of cisplatin plus cytarabine in the treatment of patients with head and neck carcinoma.
我们比较了顺铂联合氟尿嘧啶与顺铂联合阿糖胞苷在单层和多细胞肿瘤球体（MTS）系统中对HEp-2头颈部癌细胞的疗效。顺铂和氟尿嘧啶的暴露时间从1小时增加到24小时，单层细胞和MTS细胞的细胞致死率分别增加了约10倍和1000倍。顺铂或氟尿嘧啶对MTS细胞的剂量反应曲线与单层细胞的曲线密切相关，表明药物能很好地渗透到MTS核心。相比之下，顺铂和阿糖胞苷暴露24小时后，MTS细胞的剂量反应曲线显示，在较高药物浓度下疗效逐渐降低。对于单层细胞，顺铂联合氟尿嘧啶和顺铂联合阿糖胞苷均具有协同作用，后者的协同作用比前者更强。对于MTS细胞，在中等至高效应水平下，两种组合再次显示出协同相互作用。尤其是顺铂联合阿糖胞苷组合表现出更强的协同相互作用。因此，顺铂联合阿糖胞苷组合的协同作用总是比顺铂联合氟尿嘧啶更强。这些数据可为顺铂联合阿糖胞苷治疗头颈部癌患者的进一步临床试验提供依据。
