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

8110 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 ...