Juan Óscar, Aparisi Francisco, Sánchez-Hernández Alfredo, Muñoz-Langa José, Esquerdo Gaspar, García-Sánchez José, López Antonio, Garde Javier, Giner Vicente
Hospital Universitari i Politècnic La Fe, Medical Oncology Department, Valencia, Spain.
Hospital Virgen de los Lirios, Medical Oncology Department, Alcoy, Spain.
Clin Lung Cancer. 2015 May;16(3):193-9. doi: 10.1016/j.cllc.2014.11.006. Epub 2014 Nov 23.
The purpose of this study was to assess whether an intercalated dosing schedule of erlotinib and docetaxel could avoid possible negative interactions and optimize the benefit obtained as second-line therapy in non-small-cell lung cancer (NSCLC) patients.
A phase II randomized clinical trial was designed for advanced NSCLC patients in whom previous chemotherapy treatment had failed. The experimental arm with 33 patients consisted of erlotinib 150 mg/d orally, intermittent administration on days 2 to 16 every 21 days, combined with docetaxel 75 mg/m(2) every 21 days; the control arm with 35 patients consisted of erlotinib 150 mg/d orally, administered continuously. The study's primary end point was the proportion of patients who remained progression-free at 6 months in the 2 arms.
The proportion of patients who remained progression-free at 6 months was of 5 patients (15%) in the intercalated arm and 3 patients (9%) in the erlotinib monotherapy arm respectively. Median progression-free survival (PFS) was 3.0 versus 2.1 months (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.39-1.06; P = .086). Median overall survival (OS) was 7.5 and 5.2 months (HR, 0.70; 95% CI, 0.41-1.19; P = .19). Disease control rates were 51.7% and 36.4%, respectively. No new safety signals were observed.
Erlotinib and docetaxel with intermittent administration of erlotinib improved PFS, OS, and disease control rates compared with erlotinib alone. All of our results indicated that an intercalated dosing schedule of erlotinib and docetaxel could be more efficient than erlotinib treatment alone. Therefore, further studies should be developed in a larger number of patients. This study has shown the absence of antagonism between docetaxel and erlotinib when given in an intercalated fashion.
本研究的目的是评估厄洛替尼和多西他赛的间歇给药方案是否可以避免可能的负面相互作用，并优化作为非小细胞肺癌（NSCLC）患者二线治疗所获得的益处。
针对先前化疗治疗失败的晚期NSCLC患者设计了一项II期随机临床试验。试验组有33例患者，包括口服厄洛替尼150mg/d，每21天在第2至16天间歇给药，联合每21天给予多西他赛75mg/m²；对照组有35例患者，包括口服厄洛替尼150mg/d，持续给药。该研究的主要终点是两组中在6个月时无进展的患者比例。
间歇给药组和厄洛替尼单药治疗组在6个月时无进展的患者比例分别为5例（15%）和3例（9%）。中位无进展生存期（PFS）分别为3.0个月和2.1个月（风险比[HR]，0.65；95%置信区间[CI]，0.39 - 1.06；P = 0.086）。中位总生存期（OS）分别为7.5个月和5.2个月（HR，0.70；95%CI，0.41 - 1.19；P = 0.19）。疾病控制率分别为51.7%和36.4%。未观察到新的安全信号。
与单独使用厄洛替尼相比，厄洛替尼间歇给药联合多西他赛可改善PFS、OS和疾病控制率。我们所有的结果表明，厄洛替尼和多西他赛的间歇给药方案可能比单独使用厄洛替尼更有效。因此，应在更多患者中开展进一步研究。本研究表明，多西他赛和厄洛替尼以间歇方式给药时不存在拮抗作用。
