Department of Medical Oncology, National Cancer Centre, Singapore.
Ann Oncol. 2012 Apr;23(4):1010-6. doi: 10.1093/annonc/mdr327. Epub 2011 Jul 18.
Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking.
Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome.
The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome.
Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.
在体外研究中，吉非替尼与顺铂和放疗（RT）联合显示出协同作用。但在鳞状细胞头颈部癌中，预测吉非替尼反应的生物标志物仍然缺乏。
招募了 31 名局部晚期和可触及原发肿瘤部位进行活检的患者。吉非替尼在顺铂/同期放疗（CTRT）开始前 3 周开始，并在 CTRT 期间和之后的 4 个月作为巩固期继续使用。在单独使用吉非替尼 2 周后，采集了两个基线和重复肿瘤样本，以研究其对肿瘤基因表达的影响。表皮生长因子受体（EGFR）蛋白表达、FISH 和突变状态以及基质金属蛋白酶 11（MMP11）蛋白表达与反应和生存结果相关。
单独使用吉非替尼的总体反应率为 9.7%。生存结果如下：无疾病进展中位时间为 1.3 年，中位总生存期为 2.4 年，3 年无疾病进展率为 42.9%，3 年总生存率为 48.4%。EGFR FISH、蛋白表达和突变状态均不能预测患者的反应和生存结果。尽管 MMP11 过表达不能预测反应，但它确实预测了更差的生存结果。
吉非替尼可以与顺铂/RT 安全联合使用。需要更多的研究来揭示吉非替尼获益的预测生物标志物。
