Phase I/II study of intermitted erlotinib in combination with docetaxel in patients with recurrent non-small cell lung cancer (WJOG4708L).
Phase I/II study of intermitted erlotinib in combination with docetaxel in patients with recurrent non-small cell lung cancer (WJOG4708L).
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间歇性厄洛替尼联合多西他赛治疗复发性非小细胞肺癌患者的 I/II 期研究 (WJOG4708L)。
DOI：
10.1093/jjco/hyz088
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发表时间：
2019
影响因子：
2.4
通讯作者：
Nakagawa K
中科院分区：
文献类型：
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作者：
Kimura T;Kawaguchi T;Chiba Y;Yoshioka H;Watanabe K;Kijima T;Kogure Y;Oguri T;Yoshimura N;Niwa T;Kasai T;Hayashi H;Ono A;Asai K;Tanaka H;Yano S;Yamamoto N;Nakanishi Y;Nakagawa K
临床前数据表明，化疗后序贯给予表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）可能提高疗效。我们假设化疗后间歇性给药EGFR-TKI可能会提高疗效。方法：这是一项多中心、单组I/II期研究，旨在评估间歇性厄洛替尼联合多西他赛治疗一次化疗失败的gfr阴性NSCLC患者的疗效。I期研究的主要目的是确定厄洛替尼的最大耐受剂量（MTD）和推荐剂量（RD）。厄洛替尼每天口服一次，第2-16天，第1天联合60mg / m2多西紫杉醇，持续21天。厄洛替尼采用标准的3 + 3剂量递增设计，从100到150mg /剂量。II期主要终点是客观缓解率（ORR）。ORR和95%置信区间（CI）采用二项分布计算。这项研究需要45名患者。结果第一期未达到MTD，完成了计划剂量递增。厄洛替尼的RD为150mg /剂量。在II期部分，ORR和疾病控制率分别为17.1% （95%CI: 7.2-32.1%）和53.7% （95%CI: 37.4-69.3%）。中位无进展生存期和总生存期分别为3.5个月（95%CI: 3.1-4.5）和11.3个月（95%CI: 8.6-16.6）。常见的非血液学不良事件为发热性中性粒细胞减少症（3-4:19.6%）。两例治疗相关死亡是由于间质性肺病和胸膜感染。结论厄洛替尼联合多西他赛间歇给药在I期临床是可行的，但在II期没有显著改善ORR。
BackgroundPreclinical data suggest sequential administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) following chemotherapy may improve efficacy. We hypothesized that intermittent delivery of EGFR-TKI following chemotherapy may increase efficacy.MethodsThis was a multicenter, single-arm phase I/II study to evaluate the efficacy of intermitted erlotinib in combination with docetaxel in patients withEGFR-negative NSCLC who failed one prior chemotherapy. The phase I primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of erlotinib. Erlotinib was administered orally once per day on days 2–16 in combination with 60 mg/m2docetaxel on day1 for 21 days. A standard 3 + 3 dose escalation design was employed for erlotinib from 100 to 150 mg/dose. The phase II primary endpoint was the objective response rate (ORR). The ORR and 95% confidence interval (CI) were calculated using a binomial distribution. This study required 45 patients.ResultsIn the phase I part, the planned dose escalation was completed without reaching MTD. The RD of erlotinib was determined as 150 mg/dose. In the phase II part, the ORR and disease control rate were 17.1% (95%CI: 7.2–32.1%) and 53.7% (95%CI: 37.4–69.3%), respectively. Median progression-free survival and overall survival were 3.5 (95%CI: 3.1–4.5) and 11.3 (95%CI: 8.6–16.6) months, respectively. The common non-hematological adverse event was febrile neutropenia (grade 3–4:19.6%). Two treatment-related deaths were occurred because of interstitial lung disease and pleural infection.ConclusionsIntermittent dosing of erlotinib plus docetaxel is clinically feasible in phase I part but did not significantly improve ORR in phase II part.