Lb-s&t-03 a Phase 1/2 Study of Albumin-bound Rapamycin Nanoparticles in Bacillus Calmette-guerin Refractory Non-muscle Invasive Bladder Cancer
Year: 2016
Type: article
Study design: Observational Study
Abstract: You have accessJournal of UrologyLate-Breaking S&T Poster1 Apr 2016LB-S&T-03 A PHASE 1/2 STUDY OF ALBUMIN-BOUND RAPAMYCIN NANOPARTICLES IN BACILLUS CALMETTE-GUERIN REFRACTORY NON-MUSCLE INVASIVE BLADDER CANCER James McKiernan, Ifeanyi Onyeji, Danny Lascano, Jennifer Ahn, Dara Holder, Cory Abate-Shen, Arindham RoyChoudhury, and Guarionex Joel Decastro James McKiernanJames McKiernan More articles by this author , Ifeanyi OnyejiIfeanyi Onyeji More articles by this author , Danny LascanoDanny Lascano More articles by this author , Jennifer AhnJennifer Ahn More articles by this author , Dara HolderDara Holder More articles by this author , Cory Abate-ShenCory Abate-Shen More articles by this author , Arindham RoyChoudhuryArindham RoyChoudhury More articles by this author , and Guarionex Joel DecastroGuarionex Joel Decastro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.03.084AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES With the success rates of salvage therapies for non-muscle invasive bladder cancer (NMIBC) between 8-40%, novel intravesical therapies are needed to prevent progression to muscle-invasive disease. Our lab has previously demonstrated the feasibility of mTOR inhibition in mouse models of bladder cancer, so we sought to use rapamycin encapsulated in albumin-bound nanoparticles (nab-) as a potential targeted therapy for NMIBC. METHODS This phase 1 trial included patients with high-grade Ta, T1 and Tis transitional cell carcinoma of the bladder, who had failed at least 1.5 cycles of Bacillus Calmette-Guerin (BCG). Nab-rapamycin was administered weekly over 6 weeks at an initial dose of 100mg with a 3+3 dose escalation rule until the maximum tolerable dose was attained. Serum levels of the drug were monitored at each instillation. The primary endpoints were maximum deliverable dose (MDD) and dose-limiting toxicity (DLT). Efficacy was assessed by cystoscopy with biopsy and cytology at 3 months. Those without evidence of disease at 3 months received monthly maintenance at their induction dose. RESULTS Thirteen patients have completed phase 1. Characteristics of the cohort include: age (mean 73.6 years), sex (12 male, 1 female), number of prior cycles of BCG (mean 2.3), stage [cis (6), HG Ta (3), HG T1 (2), mixed LG Ta and cis (1), mixed HG T1 and cis (1)] (see Table 1). Grade 1 urinary frequency and bladder spasms were the most common local toxicities (5/13 patients each) and there were no grade 3 or higher toxicities. The mean serum drug level after instillation over the study period was 19.7 ng/dL. Two out of thirteen patients had no evidence of disease at the post-treatment cystoscopy with biopsy, and none of the patients had disease progression. CONCLUSIONS Intravesical nab-rapamycin exhibited minimal local toxicity and no systemic toxicity in this first in man clinical trial. As it appears to be safe, we are currently planning a combination phase II trial to further investigate its efficacy. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e336 Advertisement Copyright & Permissions© 2016MetricsAuthor Information James McKiernan More articles by this author Ifeanyi Onyeji More articles by this author Danny Lascano More articles by this author Jennifer Ahn More articles by this author Dara Holder More articles by this author Cory Abate-Shen More articles by this author Arindham RoyChoudhury More articles by this author Guarionex Joel Decastro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Authors: James McKiernan, Ifeanyi Onyeji, Danny Lascano, Jennifer Ahn, Dara Holder, Cory Abate-Shen, Arindham RoyChoudhury, Guarionex Joel Decastro
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2317717921