Centre Hospitalier Universitaire de Reims, Service Hépato-gastroentérologie, Hôpital Robert Debré, Avenue du Général Koenig, Reims Cedex, France.
Cancer Treat Rev. 2010 Feb;36 Suppl 1:S1-10. doi: 10.1016/S0305-7372(10)00036-8.
Despite the introduction of newer chemotherapeutic agents such as irinotecan, capecitabine and oxaliplatin, patients with metastatic colorectal cancer (mCRC) still have a poor prognosis. More effective and better-tolerated treatment strategies are needed to improve patient outcomes, particularly in subsequent lines of treatment following chemotherapy failure. The favourable efficacy and acceptable safety profiles of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have led to the approval of panitumumab and cetuximab monotherapy for the treatment of patients with EGFR-expressing mCRC whose tumours express non-mutated (wildtype) KRAS, after failure of standard chemotherapy. Cetuximab is also approved in combination with chemotherapy for the treatment of mCRC in this patient population. In phase III monotherapy studies, panitumumab and cetuximab demonstrated significant improvements in progression-free survival when administered with best supportive care (BSC) vs. BSC alone in chemotherapy-refractory mCRC patients. A planned retrospective analysis of the panitumumab monotherapy trial was the first large-scale clinical demonstration that efficacy was confined to patients with tumours expressing wild-type KRAS. It is now recognised that anti-EGFR mAb therapy should only be used in patients whose tumours express wild-type KRAS. While generally well tolerated, anti-EGFR mAb monotherapy is associated with skin toxicity, and severity of the skin rash has been proposed as an early marker of response to treatment. BRAF, PTEN, and PI3K are also emerging as future potential predictive markers of response; however, further clinical studies are warranted to define the role of these biomarkers.
尽管引入了 newer 化学治疗药物，如伊立替康、卡培他滨和奥沙利铂，转移性结直肠癌（mCRC）患者的预后仍然很差。需要更有效和耐受性更好的治疗策略来改善患者的结局，特别是在化疗失败后的后续治疗线。抗表皮生长因子受体（EGFR）单克隆抗体（mAbs）的良好疗效和可接受的安全性特征导致 panitumumab 和 cetuximab 单药治疗获批，用于治疗 EGFR 表达的 mCRC 患者，其肿瘤表达非突变（野生型）KRAS，在标准化疗失败后。cetuximab 也与化疗联合用于该患者人群的 mCRC 治疗。在 III 期单药治疗研究中，panitumumab 和 cetuximab 与最佳支持治疗（BSC）相比，在化疗耐药性 mCRC 患者中单独使用 BSC 时，显著改善了无进展生存期。panitumumab 单药治疗试验的计划回顾性分析是首次大规模临床证明疗效仅限于表达野生型 KRAS 的肿瘤患者。现在认识到，抗 EGFR mAb 治疗应仅用于表达野生型 KRAS 的肿瘤患者。尽管一般耐受性良好，但抗 EGFR mAb 单药治疗与皮肤毒性相关，皮疹的严重程度已被提议作为治疗反应的早期标志物。BRAF、PTEN 和 PI3K 也作为未来潜在的预测生物标志物出现；然而，需要进一步的临床研究来确定这些生物标志物的作用。
