Earhart R H, Neil G L
Adv Enzyme Regul. 1985;24:179-205. doi: 10.1016/0065-2571(85)90076-7.
This review, as its title indicates, views acivicin at a particular point in the ongoing process of its development. There is a large body of biochemical information which permits the formulation of a number of hypotheses regarding the drug's optimal regimen, mechanism of CNS toxicity, and potential role in combination chemotherapy. We have attempted to survey those data and to project some avenues of future research which may circumvent the drug's limitations. Current deficits exist in our information, particularly in the area of the clinical activity spectrum of acivicin. Yet the final definition of the set of human tumors in which acivicin may find clinical utility will probably not occur until we have defined the optimal regimen for the drug, both as a single agent and in combination, and have identified and addressed the toxic effects which limit its use. A coordinated effort between the preclinical pharmacologists and clinicians will be necessary in the next few years, if acivicin is to play an important role in the treatment of human malignancies.
如标题所示,本综述是在阿西维辛(acivicin)研发进程中的特定阶段对其进行审视。现有大量生化信息,据此可就该药的最佳用药方案、中枢神经系统毒性机制以及联合化疗中的潜在作用提出若干假设。我们试图梳理这些数据,并规划一些未来研究途径,以规避该药的局限性。目前我们掌握的信息存在不足,尤其是在阿西维辛临床活性谱方面。然而,在确定该药作为单一药物及联合用药的最佳方案,并识别和解决限制其使用的毒性作用之前,可能无法最终确定阿西维辛在哪些人类肿瘤中具有临床应用价值。如果阿西维辛要在人类恶性肿瘤治疗中发挥重要作用,未来几年临床前药理学家和临床医生之间需要进行协同努力。