Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus
Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus
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DOI：
10.1158/1078-0432.ccr-07-0560
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发表时间：
2007-09-01
影响因子：
11.5
通讯作者：
Miller, Vincent A.
中科院分区：
文献类型：
--
作者：
Riely, Gregory J.;Kris, Mark G.;Miller, Vincent A.
目的：10%的美国非小细胞肺癌患者对厄洛替尼或吉非替尼有部分放射学反应。尽管最初消退，这些患者发展获得性耐药厄洛替尼或吉非替尼。在这些患者中，我们试图评估停止和重新开始厄洛替尼或吉非替尼后肿瘤代谢和大小的变化，并确定添加依维莫司的效果。实验设计：非小细胞肺癌患者和获得性耐药厄洛替尼或吉非替尼是合格的。患者在基线、停用厄洛替尼或吉非替尼后3周和重新开始厄洛替尼或吉非替尼后3周进行18-氟-2-脱氧-D-葡萄糖正电子发射断层扫描/计算机断层扫描和计算机断层扫描。三周后重新开始厄洛替尼或吉非替尼，依维莫司被添加到treatment.Results：10例患者完成了所有四个计划的研究。停用厄洛替尼或吉非替尼3周后，SUVmax中位数增加18%，肿瘤直径中位数增加9%，重新开始厄洛替尼或吉非替尼3周后，SUVmax中位数下降4%，肿瘤直径中位数下降1%。无部分答复（0/10; 95%置信区间，0-31%），观察到依维莫司与厄洛替尼或吉非替尼联合使用。在发生获得性耐药的患者中，停止厄洛替尼或吉非替尼导致症状进展、SUVmax增加和肿瘤大小增加，重新开始厄洛替尼或吉非替尼后症状改善且SUVmax降低，表明一些肿瘤细胞对表皮生长因子受体阻断剂保持敏感。依维莫司和厄洛替尼或吉非替尼联合治疗未观察到缓解。我们建议进行一项随机试验来评估获得性耐药后继续使用厄洛替尼或吉非替尼的价值。
Purpose: Ten percent of U.S. patients with non-small cell lung cancer experience partial radiographic responses to erlotinib or gefitinib. Despite initial regressions, these patients develop acquired resistance to erlotinib or gefitinib. In these patients, we sought to assess changes in tumor metabolism and size after stopping and restarting erlotinib or gefitinib and to determine the effect of adding everolimus.Experimental Design: Patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib were eligible. Patients had 18-fluoro-2-deoxy--D-glucose-positron emission tomography/computed tomography and computed tomography scans at baseline, 3 weeks after stopping erlotinib or gefitinib, and 3 weeks after restarting erlotinib or gefitinib. Three weeks after restarting erlotinib or gefitinib, everolimus was added to treatment.Results: Ten patients completed all four planned studies. Three Weeks after stopping erlotinib or gefitinib, there was a median 18% increase in SUVmax and 9% increase in tumor diameter, Three weeks after restarting erlotinib or gefitinib, there was a median 4% decrease in SUVmax and 1% decrease in tumor diameter. No partial responses (0 of 10; 95% confidence interval, 0-31%) were seen with the addition of everolimus to erlotinib or gefitinib.Conclusions: In patients who develop acquired resistance, stopping erlotinib or gefitinib results in symptomatic progression, increase in SUVmax, and increase in tumor size, Symptoms improve and SUVmax decreases after restarting erlotinib or gefitinib, suggesting that some tumor cells remain sensitive to epidermal growth factor receptor blockade. No responses were observed with combined everolimus and erlotinib or gefitinib. We recommend a randomized trial to assess the value of continuing erlotinib or gefitinib after development of acquired resistance.