ABSTRACT
PURPOSE: Brain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety. PATIENTS AND METHODS: Eligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility. RESULTS: Forty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n = 36). No increase in neurotoxicity was detected, and no patient experienced grade ≥ 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations. CONCLUSION: Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.
Subject(s)
Antineoplastic Agents/therapeutic use , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Non-Small-Cell Lung/therapy , Cranial Irradiation , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Lung Neoplasms/pathology , Mutation , Quinazolines/therapeutic use , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Chemoradiotherapy , Drug Administration Schedule , Drug Eruptions/etiology , Erlotinib Hydrochloride , Female , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Quinazolines/administration & dosage , Quinazolines/adverse effects , Treatment OutcomeABSTRACT
Echocardiography is comparatively inexpensive relative to other modern cardiovascular imaging tools. It is widely available, even in poor countries, and provides a comprehensive evaluation of cardiac structure and function. It is an ideal tool for the evaluation of patients with valvular heart disease and provides important prognostic information. This review of recent literature highlights reports on outcomes data and provides a clinically valuable summary in table format.
