Medical Oncology Department, University Hospital 12 de Octubre, Avda. de Andalucía s/n Km 5.400, Madrid, Spain.
Crit Rev Oncol Hematol. 2010 Apr;74(1):16-26. doi: 10.1016/j.critrevonc.2009.06.005. Epub 2009 Jul 17.
Conventional chemotherapy increases progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients versus best supportive care (BSC). However, the efficacy of chemotherapy is limited. Recently approved monoclonal antibodies (MoAb) have a different mechanism of action, targeting growth factors or their receptors. Panitumumab is a fully human IgG2 MoAb directed against the epidermal growth factor receptor (EGFR). In phase II trials, panitumumab showed preliminary activity in chemorefractory mCRC. This efficacy was confirmed in a randomized pivotal phase III trial, which compared single-agent panitumumab plus BSC versus BSC alone. Several ongoing clinical trials are evaluating panitumumab in combination with different chemotherapy regimens in first- and second-line settings. Skin toxicities, hypomagnesemia, and diarrhea are the most common adverse events associated with anti-EGFR therapy. KRAS status and skin rash have been correlated with panitumumab efficacy. This article reviews the preclinical and pharmacokinetics data, activity and tolerance of panitumumab in mCRC patients. Potential predictive factors of response are also discussed.
传统化疗可提高转移性结直肠癌（mCRC）患者的无进展生存期（PFS）和总生存期（OS），优于最佳支持治疗（BSC）。然而，化疗的疗效有限。最近批准的单克隆抗体（MoAb）具有不同的作用机制，针对生长因子或其受体。帕尼单抗是一种针对表皮生长因子受体（EGFR）的完全人源 IgG2 MoAb。在 II 期试验中，帕尼单抗在化疗耐药的 mCRC 中显示出初步疗效。一项随机关键 III 期试验证实了这一疗效，该试验比较了单药帕尼单抗加 BSC 与单独 BSC。目前正在进行多项临床试验，评估帕尼单抗联合不同化疗方案在一线和二线治疗中的疗效。皮肤毒性、低镁血症和腹泻是与抗 EGFR 治疗相关的最常见不良反应。KRAS 状态和皮疹与帕尼单抗的疗效相关。本文综述了帕尼单抗在 mCRC 患者中的临床前和药代动力学数据、疗效和耐受性，还讨论了潜在的预测反应的因素。
