Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy

Background: The majority of urothelial cancers (UC) harbor alterations in retinoblastoma (Rb) pathway genes that can lead to loss of Rb tumour suppressor function. Palbociclib is an oral, selective inhibitor of CDK 4/6 that restores Rb function and promotes cell cycle arrest. Methods: In this phase II trial, patients with metastatic platinum-refractory UC molecularly selected for p16 loss and intact Rb by tumour immunohistochemistry received palbociclib 125 mg p.o. daily for 21 days of a 28-day cycle. Primary endpoint was progression-free survival at 4 months (PFS4) using a Simon’s two-stage design. Next-generation sequencing including Rb pathway alterations was conducted. Results: Twelve patients were enrolled and two patients (17%) achieved PFS4 with insufficient activity to advance to stage 2. No responses were seen. Median PFS was 1.9 months (95% CI 1.8–3.7 months) and median overall survival was 6.3 months (95% CI 2.2–12.6 months). Fifty-eight percent of patients had grade ≥3 hematologic toxicity. There were no CDKN2A alterations found and no correlation of Rb pathway alterations with clinical outcome. Conclusions: Palbociclib did not demonstrate meaningful activity in selected patients with platinum-refractory metastatic UC. Further development of palbociclib should only be considered with improved integral biomarker selection or in rational combination with other therapies

Adoption of managerial ideologies in Finnish academic management education 1960-2007

The article analyses when and how different management paradigms have been adopted for teaching, in the subject of organization and management, by examining the curricula and study guides of the eight main business schools in Finland.The data was analysed in three ways: (1) the analysis of all the reading lists in curricula and study guides, (2) the analyses of subject descriptions in the study guides and (3) the analysis of individual course descriptions in the study guides.Theoretically, the study draws on the literature on German-style and American-style business schools, and on the literature on management paradigms and their dissemination.Our findings indicate that there are differences in the adoption of different management paradigms in management education in German-style and American-style business schools in Finland. For example, between 1980 and 1995, the most commonly used paradigm in teaching in German-style schools was the human relations paradigm, while in American-style schools the most popular paradigm was structural analysis.The results suggest that different traditions in arranging higher management education may have an impact on the content of teaching.This provides an interesting point of departure for investigating the contents of management education in other countries, too