Bioconjugates Discovery and Development, Oncology Research Unit, Pfizer Worldwide Research and Development, Pearl River, NY, 10965, USA.
Expert Rev Clin Pharmacol. 2013 Sep;6(5):541-55. doi: 10.1586/17512433.2013.827405. Epub 2013 Aug 26.
Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for the clinical management of cancer. Here we discuss the clinical pharmacology and safety of ADCs that are either approved or in late stages of clinical development. We have taken examples of ADCs employing either DNA damaging payloads (such as calicheamicin) or tubulin depolymerizing agents (such as auristatins and maytansinoids) to discuss the impact of dose and dosage intervals on pharmacokinetics/pharmacodynamics (PK/PD) and safety of ADCs. We also discuss the development of PK/PD models that were validated using preclinical and clinical data from two approved ADCs (ado-trastuzumab emtansine (T-DM1, Kadcyla™) and brentuximab vedotin (SGN-35, Adcetris™). These models could be used to predict clinical efficacious doses of ADCs.
抗体药物偶联物（ADC）代表了癌症临床治疗的一种很有前途的治疗方式。在这里，我们讨论了已批准或处于临床开发后期的 ADC 的临床药理学和安全性。我们以使用 DNA 损伤有效载荷（如加利昔单抗）或微管去聚合剂（如 Auristatins 和 Maytansinoids）的 ADC 为例，讨论了剂量和剂量间隔对 ADC 的药代动力学/药效学（PK/PD）和安全性的影响。我们还讨论了使用来自两种已批准 ADC（ado-trastuzumab emtansine（T-DM1，Kadcyla™）和 brentuximab vedotin（SGN-35，Adcetris™）的临床前和临床数据验证的 PK/PD 模型的开发。这些模型可用于预测 ADC 的临床有效剂量。
