2014ASCO年会摘要发布

costa_na · 发表于 2014-5-15 12:49:35

Phase I trial of icotinib combined with whole brain radiotherapy for EGFR-mutated non-small cell lung cancer patients with brain metastases.

Abstract:

Background: Icotinib has been demonstrated to provide similar efficacy to gefitinib in non-small cell lung cancer (NSCLC) patients. This phase I trial (NCT01516983) evaluated the dose-escalation toxicity of icotinib combined with whole brain radiotherapy (WBRT) in EGFR-mutated NSCLC patients with brain metastases, and cerebrospinal fluid (CSF) penetration rates of icotinib were assessed in the dose-escalation.

Methods: The cohorts were constructed with a 3 + 3 design, and the dose-escalation schedule of icotinib was set as 125mg tid, 250mg tid, 375mg tid, 500mg tid, and 625mg tid. Icotinib was started 7 days before and continued during WBRT (37.5Gy/15f/21d), and maintained until disease progression or intolerable toxicities occurred. The blood and CSF samples were obtained at 7:30-8:00 a.m. just before the administration of icotinib on day 7 (before WBRT), day 29 (after WBRT) and day 57 of therapy.

Results: Fifteen patients were enrolled in this trial. The treatment-related toxicities were generally mild (CTC AE grade 1-2), and the most frequent treatment-related toxicities were alopecia (15/15), acne-like rash (14/15) and nausea (11/15). At dose level of 500mg tid, 3 out of 6 patients experienced dose-limiting toxicity including 1 grade 3 alanine aminotransferase elevation and 2 grade 3 nausea, after reducing the dose of icotinib to 250mg tid, these toxicities disappeared. The mean icotinib CSF penetration rate was 4.04% (range: 1.23%-9.71%), and there was a good correlation between plasma and CSF concentrations (R2=0.577, P<0.001). There were no statistical differences in plasma concentrations, CSF concentrations, and penetration rates of icotinib between day 7, day 29, and day 57. However, CSF concentration and penetration rate of icotinib were much higher at dose of 375mg tid (mean CSF concentration: 154.09ng/ml, P<0.001; mean penetration rate: 7.06%, P<0.001).

Conclusions: WBRT with concurrent and maintenance icotinib (125mg tid-375mg tid) were well tolerated in EGFR-mutated NSCLC patients with brain metastases. WBRT might not increase penetration rate of icotinib, however, there were the highest CSF concentration and penetration rate at dose of 375mg tid. Clinical trial information: NCT01516983.