A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. RESULTS: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.

Dementia Pugilistica with Clinical Features of Frontotemporal Dementia and Parkinsonism: Case Report

Dementia pugilistica (DP) or chronic traumatic encephalopathy (CTE) is a neurodegenerative disease or dementia that may affect amateur or professional boxers as well as athletes in other sports who suffer concussions. The condition is thought to affect around 15% to 20% of professional boxers and caused by repeated concussive or subconcussive blows. CTE was in the past referred to as dementia pugilistica, which reflected the prevailing notion that this condition was restricted to boxers. Recent research, however, has demonstrated neuropathological evidence of CTE in retired American football players, a professional wrestler, a professional hockey player and a soccer player, as well as in nonathletes. It is probable that many individuals are susceptible to CTE, including those who experience falls, motor vehicle accidents, assaults, epileptic seizures, or military combat, and that repeated mild closed head trauma of diverse origin is capable of instigating the neurodegenerative cascade leading to CTE. We report a 62-year old man suspicious of dementia pugilistica with clinical features of frontotemporal dementia and parkinsonism.