Schmoll H J, Niederle N, Achterrath W
Klin Wochenschr. 1981 Nov 2;59(21):1177-88. doi: 10.1007/BF01721212.
Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal with cis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80--120 mg/m2 on 3--5 consecutive days and repetition after 21 [14--28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.
依托泊苷是一种半合成的鬼臼毒素衍生物,具有广泛的抗肿瘤活性和相对较高的治疗指数。在动物实验中,它与顺铂、环磷酰胺、卡氮芥和阿糖胞苷具有协同作用,这对于联合用药方案来说很有意义。其作用机制包括抑制核苷转移以及DNA和RNA合成、造成单链断裂、抑制蛋白质合成和微管组装。在较低浓度时,依托泊苷的作用具有细胞周期依赖性,可使细胞在G2期蓄积;而在高浓度时,它也具有细胞周期非特异性致死作用。依托泊苷最适宜的给药方式是口服和静脉注射,分次给药,剂量为80 - 120mg/m²,连续3 - 5天,21[14 - 28]天后重复给药。副作用包括剂量限制性骨髓毒性、恶心、呕吐、发热、低血压、静脉炎、粘膜炎、神经病变、心脏毒性、脱发。依托泊苷是小细胞支气管癌中最有效的单一药物之一,缓解率为37%(完全缓解率为10%),在非霍奇金淋巴瘤(36%)、睾丸癌(37%)、急性髓性单核细胞白血病(35%)、绒毛膜癌(35%)和神经母细胞瘤(29%)中也非常有效。目前正在支气管癌、睾丸癌和非霍奇金淋巴瘤中研究依托泊苷与其他活性药物联合用于这些肿瘤的作用,未来依托泊苷将成为首选药物之一。