Critical Appraisal of Gefitinib in the Treatment of Non-Small Cell Lung Cancer

Gefitinib於非小細胞肺癌治療之關鍵評論

羅永鴻(Yung-Hung Luo) ； 李毓芹(Yu-Chin Lee) ； 彭汪嘉康(Jacqueline Whang-Peng) ； 陳育民(Yuh-Min Chen)

《台灣癌症醫學雜誌》 2卷3期 (2015/09) Pp. 179-194

https://doi.org/10.6323/JCRP.2015.2.3.01

摘要

肺癌為全世界惡性腫瘤死亡率最高之癌症。在分子標靶治療發展出來以前，以platinum為主的合併化學藥物治療（doublets）是晚期非小細胞肺癌的第一線標準治療。自從有了上皮細胞生長因素接收器-酪胺酸酶抑制劑（epidermal growth factor receptor-tyrosine kinase inhibitor，EGFR-TKI）之後，非小細胞肺癌的治療便有了長足之進展。EGFR基因有exon 19突變（deletion），或exon 21突變（L858R point mutation）之患者對EGFR-TKI 的藥效反應相當地好。所以對於每一位非小細胞肺癌的患者，臨床醫師應該要盡力去檢測出患者的EGFR基因之突變狀態，以找出適合EGFR-TKI治療之病人。第一代的EGFR-TKIs，包括gefitinib與erlotinib。Gefitinib是第一個發展出來治療非小細胞肺癌的EGFR-TKI。一些隨機分配之第三期臨床試驗顯示，gefitinib與合併化學藥物治療相比之下，對於有EGFR基因活化性突變的晚期非小細胞肺癌，具有較好的藥效反應、較好的無疾病惡化存活期、及較少的副作用。目前，gefitinib是具有EGFR基因突變的晚期非小細胞肺癌之第一線治療藥物。Gefitinib也可作為接受過化學治療的非小細胞肺癌患者之挽救性治療。對於野生型EGFR之患者，或者是EGFR基因突變狀態不明之患者，以platinum為主的合併化學藥物治療仍然是第一線標準治療。本篇文章回顧了Gefitinib作為分子標靶治療之相關臨床研究。

關鍵字

非小細胞肺癌 ； 上皮細胞生長因素接收器 ； 酪胺酸酶抑制劑

並列摘要

The leading cause of death from malignant tumors worldwide is lung cancer. Before the development of molecularly targeted therapy, chemotherapy with platinum-based doublets was considered as the standard first-line treatment in advanced non-small cell lung cancer (NSCLC) patients. The introduction of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has led to remarkable advances in the treatment of NSCLC. Two activating EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation) have been correlated with dramatic responses to EGFR-TKI. Every effort should be made to identify the EGFR mutation status in NSCLC patients prior to the initial systemic treatment in order to select those who are most likely to benefit from EGFR-TKIs. At the present time, first-generation EGFR-TKIs are available for clinical use, including gefitinib and erlotinib. Gefitinib was the first drug developed as an EGFR-TKI for NSCLC treatment. Several randomized phase III studies revealed that gefitinib provided superior response rate, improved PFS, and less toxicity compared with doublet chemotherapy for advanced NSCLC with activating EGFR mutation. Currently, first-line treatment with gefitinib is used in metastatic NSCLC patients with tumor EGFR mutation. Gefitinib is also administered as salvage therapy for NSCLC patients previously treated with chemotherapy. The standard of care for previously untreated patients with EGFR mutation-negative or unknown status still remains platinum-based chemotherapy. In this article, we have reviewed the relevant clinical data regarding gefitinib as a molecularly targeted therapy for NSCLC.

並列關鍵字

gefitinib ； non-small cell lung cancer ； epidermal growth factor receptor ； tyrosine kinase inhibitor