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Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer
Vivek Narayan,Ronac Mamtani,Stephen Keefe,Thomas Guzzo,S. Bruce Malkowicz,David J. Vaughn 대한암학회 2016 Cancer Research and Treatment Vol.48 No.3
Purpose We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Materials and Methods Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. Results The initial four patients received gemcitabine 1,000 mg/m2 intravenously on days 1 and 8 and cisplatin 70 mg/m2 intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). Conclusion The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.
Malavasi, N.,Arnouts, S.,Vibert, D.,de la Torre, S.,Moutard, T.,Pichon, C.,Davidzon, I.,Kraljic, K.,Bolzonella, M.,Guzzo, L.,Garilli, B.,Scodeggio, M.,Granett, B. R.,Abbas, U.,Adami, C.,Bottini, D.,Ca Oxford University Press 2017 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.465 No.4
<P>We present the first quantitative detection of large-scale filamentary structure at z similar or equal to 0.7 in the large cosmological volume probed by the VIMOS Public Extragalactic Redshift Survey (VIPERS). We use simulations to show the capability of VIPERS to recover robust topological features in the galaxy distribution, in particular the filamentary network. We then investigate how galaxies with different stellar masses and stellar activities are distributed around the filaments, and find a significant segregation, with the most massive or quiescent galaxies being closer to the filament axis than less massive or active galaxies. The signal persists even after downweighting the contribution of peak regions. Our results suggest that massive and quiescent galaxies assemble their stellar mass through successive mergers during their migration along filaments towards the nodes of the cosmic web. On the other hand, low-mass star-forming galaxies prefer the outer edge of filaments, a vorticity-rich region dominated by smooth accretion, as predicted by the recent spin alignment theory. This emphasizes the role of large-scale cosmic flows in shaping galaxy properties.</P>