Design paper: A phase II study of Bevacizumab and Erlotinib in patients with non-Squamous non-small cell lung cancer that is refractory or relapsed after 1-2 previous Treatment (BEST)

<p>Abstract</p> <p>Background</p> <p>Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.</p> <p>Methods</p> <p>Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.</p> <p>Discussion</p> <p>We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.</p> <p>Trial registration</p> <p>This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (<url>http://www.umin.ac.jp/ctr/index.htm</url>).</p

Case Reports of Unexpected Suicides in Patients within Six Months after Stroke

ABSTRACT Suicide after stroke is a grievous occurrence. Since the majority of cases under study had shown signs of recovery from stroke, persons surrounding these patients were severely shocked by these suicides. Six patients who attempted suicide within six months after stroke were investigated to determine factors following stroke that relate to suicide in order to prevent future post-stroke suicides. Clinical findings in these six cases were retrospectively analyzed in collaboration with stroke neurologists and coworkers caring for these patients. Four of six patients had sustained a recent infarction extending from the temporal cortex to the parietal cortex. Four of six patients showed depression, and five of six patients showed moderate disability after stroke. Physicians should carefully observe patients with infarction extending from the temporal cortex to the parietal cortex, depression and moderate disability, in order to prevent suicidal behavior. INTRODUCTION The underlying causes of suicide have generally been associated with social situations (1), mental problems (2, 3) and genetics (4). To date, several studies of brain abnormalities related to suicide analyzed postmortem findings in suicide victims (5-7). These studies showed that disorders of the serotonergic system in the prefrontal cortex and brain stem are key issues in suicidal behavior. Furthermore, patients with temporal lobe epilepsy have been reported to show a tendency toward suicide attempts (8-10). Stroke patients commonly develop depression and may have suicidal ideation (11-16), but rarely attempt suicide in the early stage following stroke (17). We analyzed and compared six patients who attempted suicide within six months after stroke, and discuss measures to prevent suicide