A Phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer
A Phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer
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DOI：
10.1002/cncr.22088
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发表时间：
2006-09-01
期刊：
影响因子：
6.2
通讯作者：
Miller, Vincent A.
中科院分区：
文献类型：
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作者：
Milton, Daniel I.;Azzoli, Christopher G.;Miller, Vincent A.
背景临床前研究表明，高剂量厄洛替尼可能抑制表皮生长因子受体（EGFR）下游的其他位点，从而产生更大的抗肿瘤疗效。本研究的目的是确定大剂量厄洛替尼每周一次给药对晚期非小细胞肺癌（NSCLC）患者的耐受性和疗效。作者在既往接受过化疗的进展性NSCLC患者中进行了每周一次厄洛替尼的I/II期试验。在I期部分，患者入组3个患者队列，厄洛替尼剂量水平为1200 mg、1600 mg和2000 mg，每周一次。11期部分旨在确定试验I期部分确定的剂量的主要客观缓解率。27例患者入组。未观察到剂量限制性毒性。I级和2级皮疹和腹泻是主要的毒性反应，各发生在92%的患者中。在21例接受11期剂量2000 mg每周一次治疗的患者中，确定了单一客观缓解，缓解率为5%（95%置信区间，0.2-22%）。对于该队列，中位生存期为9.5个月。唯一的放射学缓解发生在治疗前肿瘤标本携带EGFR外显子19缺失的患者中。这些晚期NSCLC患者对厄洛替尼2000 mg每周一次给药的耐受性良好。在中期疗效分析时，5%的客观缓解率未达到规定的目标，促使研究关闭。
BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC).METHODS. The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotimb dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly The Phase 11 portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial.RESULTS. Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade I and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase 11 dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2-22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion.CONCLUSIONS. Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study.