Abstract：
Vincristine (VCR), an effective antitumor drug, has been utilized in several polytherapy regimens for acute lymphoblastic leukemia, neuroblastoma and rhabdomyosarcoma. However, clinical evidence shows that the metabolism of VCR varies greatly among patients. The traditional based body surface area (BSA) administration method is prone to insufficient exposure to VCR or severe VCR-induced peripheral neurotoxicity (VIPN). Therefore, reliable strategies are urgently needed to improve efficacy and reduce VIPN. Due to the unpredictable pharmacokinetic changes of VCR, therapeutic drug monitoring (TDM) may help to ensure its efficacy and to manage VIPN. At present, there is a lot of supporting evidence for the suitability of applying TDM to VCR therapy. Based on the consensus guidelines drafted by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), this review aimed to summarize various available data to evaluate the potential utility of VCR TDM for cancer patients. Of note, valuable evidence has accumulated on pharmacokinetics variability, pharmacodynamics, drug exposure-clinical response relationship, biomarkers for VIPN prediction, and assays for VCR monitoring. However, there are still many relevant clinical pharmacological questions that cannot yet be answered merely based on insufficient evidence. Currently, we cannot recommend a therapeutic exposure range and cannot yet provide a dose-adaptation strategy for clinicians and patients. In areas where the evidence is not yet sufficient, more research is needed in the future. The precision medicine of VCR cannot rely on TDM alone and needs to consider the clinical, environmental, genetic background and patient-specific factors as a whole.
摘要：
长春新碱(VCR)一种有效的抗肿瘤药物，已经在几种急性淋巴细胞白血病的综合治疗方案中使用，神经母细胞瘤和横纹肌肉瘤。然而,临床证据表明，VCR的代谢在患者之间差异很大。传统的基于体表面积（BSA）的给药方法易于对VCR的暴露不足或严重的VCR诱导的周围神经毒性（VIPN）。因此,迫切需要可靠的策略来提高疗效并减少VIPN。由于VCR的不可预测的药代动力学变化，治疗药物监测（TDM）可能有助于确保其疗效并管理VIPN。目前,有大量支持证据证明TDM适用于VCR治疗.根据国际治疗药物监测和临床毒理学协会（IATDMCT）起草的共识指南，这篇综述旨在总结各种可用数据，以评估VCRTDM对癌症患者的潜在效用。值得注意的是，已经积累了关于药代动力学变异性的宝贵证据，药效学,药物暴露-临床反应关系，用于VIPN预测的生物标志物，和VCR监测的测定。然而,仍然有许多相关的临床药理问题，尚不能仅仅基于不足的证据来回答。目前,我们无法推荐治疗暴露范围,也无法为临床医师和患者提供剂量适应策略.在证据不足的地区,未来需要更多的研究。VCR的精准医疗不能单靠TDM,需要考虑临床,环境,遗传背景和患者特异性因素作为一个整体。
