ZD1839 (Gefinitib, Iressa) In Patients With Non Small Cell Lung Cancer: A Real Promise?

A. Tartarone, G. Romano, R. Ardito, N. Renzo
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Abstract

ZD 1839 is a novel, low molecular weight, orally active, selective EGFR-tyrosine kinase inhibitor, which in preclinical and phase I studies has showed antitumor activity against cancers expressing EGFR. Phase I-II studies showed that ZD 1839 provides clinically significant antitumor activity in patients with pretreated NSCLC. Subsequently, phase III trials combined ZD1839 and chemotherapy in chemonaive patients with advanced NSCLC. These trials failed to demonstrate a survival advantage with the addition of ZD1839 to standard platinum-based chemotherapy. Some experts have suggested that the concomitant administration of chemotherapy and EGFR tyrosine kinase inhibitors may be antagonistic and that sequential use of these drug is a more appropriate strategy. The molecular mechanisms underlying sensitivity to ZD1839 are unknown, however recent preliminary experiences suggest that EGFR mutations may predict sensitivity to ZD1839. In any case, future trials should be conducted with appropriate correlative studies in diagnostic tumor tissue and a new possible area of clinical investigation include the use of ZD1839 in adjuvant setting.
ZD1839(吉非尼替、易瑞沙)治疗非小细胞肺癌:真正的希望?
zd1839是一种新型的低分子量、口服活性、选择性EGFR-酪氨酸激酶抑制剂,在临床前和I期研究中显示出对表达EGFR的癌症的抗肿瘤活性。I-II期研究表明,ZD 1839对经预处理的NSCLC患者具有临床显著的抗肿瘤活性。随后,III期试验将ZD1839和化疗联合用于晚期NSCLC化疗患者。这些试验未能证明在标准铂基化疗中添加ZD1839具有生存优势。一些专家建议,同时使用化疗和EGFR酪氨酸激酶抑制剂可能是拮抗的,顺序使用这些药物是更合适的策略。对ZD1839敏感性的分子机制尚不清楚,但最近的初步经验表明,EGFR突变可能预测对ZD1839的敏感性。无论如何,未来的试验应该在诊断肿瘤组织中进行适当的相关研究,并且一个新的可能的临床研究领域包括在辅助环境中使用ZD1839。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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