Phase II study of dual phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma (TCC)

BJU International
E SerontJ-P Machiels

Abstract

Excessive activation of the PI3K/Akt/mTOR pathway is frequently observed in transitional cell carcinoma (TCC) due to a loss of PTEN and/or activating mutation of PIK3CA. Allosteric mTOR inhibition by everolimus resulted in modest efficacy in advanced TCC. In different TCC cell lines, it has been shown that PI3K inhibition enhanced the efficacy of mTOR inhibitors with a synergistic effect observed mainly in cells with PI3K/Akt/mTOR pathway alterations. To assess in a multicenter phase II trial the safety and efficacy of BEZ235, an oral pan-class I PI3K and mTOR complex1/2 inhibitor, in locally advanced or metastatic TCC after failure of platinum-based therapy. Patients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All received BEZ235 until progressive disease (PD) or unacceptable toxicity. The primary endpoint was the progression free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely due to BEZ235 being withdrawn from further development. Twenty patients (18 without and two with PI3K/Akt/mTOR alterations) were enrolled and received BEZ235. One partial response (5%) ...Continue Reading

References

May 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J A McCaffreyD F Bajorin
Nov 5, 1997·American Journal of Clinical Oncology·P PronzatoF Vaira
Dec 16, 1998·Investigational New Drugs·R S WitteP J Loehrer
Dec 16, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·V LorussoM De Lena
Jun 9, 1999·British Journal of Cancer·J S AveyardM A Knowles
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S NeshatC L Sawyers
Jul 22, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hans von der MaaseMichael Arning
Feb 3, 2006·Cancer Research·Kathryn E O'ReillyNeal Rosen
Dec 6, 2006·Investigational New Drugs·Matthew D GalskyDean F Bajorin
Jun 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maha H A HussainUNKNOWN National Cancer Institute
Aug 19, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joaquim BellmuntHans von der Maase
Dec 17, 2009·Cancer Metastasis Reviews·Margaret A KnowlesCarolyn D Hurst
Feb 10, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David J GallagherDean F Bajorin
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joaquim BellmuntJonathan E Rosenberg
Oct 12, 2010·Applied Immunohistochemistry & Molecular Morphology : AIMM·Zaina SangaleSteven Stone
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Mar 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Funda Meric-BernstamJames Yao
Aug 29, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yu-Ning WongGary Hudes
Jan 31, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network

❮ Previous
Next ❯

Citations

Feb 25, 2018·The Journal of Biological Chemistry·Grant R CampbellStephen A Spector
Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Giuseppe Curigliano, Rashmi R Shah
Mar 11, 2018·Clinical Science·Alberto M MartelliJames A McCubrey
Jun 24, 2016·Nature Reviews. Rheumatology·Jason S Rockel, Mohit Kapoor
Dec 11, 2019·Cells·Cedric MagawayEstela Jacinto
Mar 7, 2020·ESMO Open·Elizabeth Liow, Ben Tran
Aug 12, 2018·International Journal of Molecular Sciences·Hannah E Walters, Lynne S Cox
Jan 24, 2019·Therapeutic Advances in Urology·Maristella BianconiRodolfo Montironi
Feb 16, 2021·Frontiers in Oncology·Mei PengXiaoping Yang
Jan 17, 2021·International Journal of Molecular Sciences·Javier Torres-JiménezJavier Molina-Cerrillo
Mar 30, 2021·Frontiers in Oncology·Miguel Olivas-AguirreOxana Dobrovinskaya
May 8, 2021·Hematology/oncology Clinics of North America·Brendan J GuercioJonathan E Rosenberg
Jul 6, 2021·Frontiers in Oncology·Ricardo Rivera-SotoBlossom Damania

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Related Papers

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Amit M OzaFrank G Haluska
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Toshihiko DoiAtsushi Ohtsu
Annals of Oncology : Official Journal of the European Society for Medical Oncology
S M LimB C Cho
© 2022 Meta ULC. All rights reserved