A phase II study of lapatinib,a dual EGFR and HER-2 tyrosine kinase inhibitor,in patients with castration-resistant prostate cancer

ObjectivesEpidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer.MethodsIn this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes.ResultsTwenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days.ConclusionsLapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.     

Diagnosis and Medical Management of Multiple Sclerosis

Abstract

Background: This case report describes a neuroprosthesis that restored shoulder and elbow function in a 23-year-old man with chronic C3 complete tetraplegia. Before implementation of the neuroprosthesis, electrodiagnostic testing revealed denervation from CS to T1, with the greatest degree of denervation in the C8 and T1 myotomes. Thirteen percutaneous intramuscular electrodes were implanted into muscles acting on the shoulder and elbow of one upper limb. Before functional testing, the subject underwent a conditioning regimen to maximize the strength and endurance of the implanted muscles.

Results: After completion of the 8-week exercise regimen, stimulated active range of motion against gravity included 60° of shoulder abduction, 45° of shoulder flexion, 10° of shoulder external rotation with the shoulder passively abducted to 90°, and 110° of elbow flexion. Stimulated elbow extension lacked 20° of full extension with gravity eliminated. After system setup, the subject was able to pick up mashed potatoes on a plate with a utensil and bring them to his mouth using the neuroprosthesis and a balanced forearm orthosis. A switch mounted on the headrest of the subject's wheelchair and a position sensor mounted on the co tralateral shoulder allowed the subject to control movement of his upper limb.     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.