Ohkubo T, Higashigawa M, Kawasaki H, Kamiya H, Sakurai M, Kagawa Y, Kakito E, Sumida K, Ooi K
Department of Pediatrics, Mie University, School of Medicine, Japan.
Eur J Cancer Clin Oncol. 1988 Dec;24(12):1823-8. doi: 10.1016/0277-5379(88)90092-2.
The sequence-dependence of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated against the L1210 ascites tumor in BDF1 mice. Treatment with VP16 (7.5 or 15 mg/kg) and ara-C (25 or 500 mg/kg) was administered intraperitoneally on days 1, 4 and 7 after tumor inoculation. Six hour pretreatment with 15 mg/kg VP16 followed by 500 mg/kg ara-C yielded a 100% cure rate, but only a 20% cure rate was obtained with the reverse sequence. Simultaneous administration of 15 mg/kg of VP-16 and 500 mg/kg ara-C interacted synergistically, producing a 70% cure rate. In contrast with the results obtained with VP-16 and 500 mg/kg ara-C, simultaneous administration of 25 mg/kg ara-C neither antagonized nor potentiated the antitumor effect of VP-16. Twenty-five mg/kg ara-C was too low to produce any antitumor effect with VP-16 in simultaneous administration. At every dose investigated, pretreatment with VP-16 followed by ara-C was the most effective antitumor schedule in L1210 leukemia. This sequence of drug administration did not cause greater toxicity as measured by weight loss or toxic death.
研究了依托泊苷（VP - 16）和1 - β - D - 阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara - C）对BDF1小鼠L1210腹水瘤抗肿瘤作用的序列依赖性。在接种肿瘤后的第1、4和7天腹腔注射VP16（7.5或15mg/kg）和阿糖胞苷（25或500mg/kg）。先用15mg/kg VP16预处理6小时，随后给予500mg/kg阿糖胞苷，治愈率为100%，但顺序相反时治愈率仅为20%。同时给予15mg/kg的VP - 16和500mg/kg阿糖胞苷产生协同作用，治愈率为70%。与VP - 16和500mg/kg阿糖胞苷的结果相反，同时给予25mg/kg阿糖胞苷既不拮抗也不增强VP - 16的抗肿瘤作用。25mg/kg阿糖胞苷剂量过低，与VP - 16同时给药时不会产生任何抗肿瘤作用。在所研究的每一个剂量下，先用VP - 16预处理再给予阿糖胞苷是L1210白血病最有效的抗肿瘤给药方案。这种给药顺序并未导致以体重减轻或毒性死亡衡量的更大毒性。
