Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Clin Pharmacokinet. 2018 Apr;57(4):455-473. doi: 10.1007/s40262-017-0590-9.
Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mCRC. Panitumumab is used in different lines of therapy in combination with chemotherapy, and as monotherapy for the treatment of wild-type (WT) RAS mCRC. It is administered as an intravenous infusion of 6 mg/kg every 2 weeks and has a t of approximately 7.5 days. Elimination takes place via two different mechanisms, and immunogenicity rates are low. Only RAS mutations have been confirmed as a negative predictor of efficacy with anti-EGFR antibodies. Panitumumab is generally well tolerated and has a manageable toxicity profile, despite a very high prevalence of dermatologic side effects. This article presents an overview of the clinical pharmacokinetics and pharmacodynamics of panitumumab, including a description of the studies that led to its approval in the different lines of therapy of mCRC.
尽管在过去 15 年中转移性结直肠癌（mCRC）的治疗取得了进展，但它仍然是一种 5 年生存率相对较低的疾病。帕尼单抗是一种针对表皮生长因子受体（EGFR）的全人源单克隆抗体，能够延长 mCRC 患者的生存时间。帕尼单抗可与化疗联合用于不同的治疗线，也可作为野生型（WT）RAS mCRC 的单药治疗。它以 6mg/kg 的剂量静脉输注，每 2 周一次，t 约为 7.5 天。消除通过两种不同的机制发生，免疫原性率较低。只有 RAS 突变被证实是抗 EGFR 抗体疗效的负预测因子。尽管皮肤毒性副作用的发生率很高，但帕尼单抗总体上耐受性良好，且毒性谱易于管理。本文介绍了帕尼单抗的临床药代动力学和药效学概述，包括导致其在 mCRC 不同治疗线中获得批准的研究描述。
