Cargando…
Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer
BACKGROUND: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. OBJECTIVE: To evalu...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087454/ https://www.ncbi.nlm.nih.gov/pubmed/30112440 http://dx.doi.org/10.3233/BLC-180166 |
_version_ | 1783346689572077568 |
---|---|
author | Karsh, Lawrence Shore, Neal Soloway, Mark Bhat, Gajanan Reddy, Guru Leu, Szu-Yun Witjes, J. Alfred |
author_facet | Karsh, Lawrence Shore, Neal Soloway, Mark Bhat, Gajanan Reddy, Guru Leu, Szu-Yun Witjes, J. Alfred |
author_sort | Karsh, Lawrence |
collection | PubMed |
description | BACKGROUND: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. OBJECTIVE: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. METHODS: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively. RESULTS: Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60±30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity. CONCLUSIONS: Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60±30-minutes time interval which requires further study. |
format | Online Article Text |
id | pubmed-6087454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60874542018-08-13 Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer Karsh, Lawrence Shore, Neal Soloway, Mark Bhat, Gajanan Reddy, Guru Leu, Szu-Yun Witjes, J. Alfred Bladder Cancer Research Report BACKGROUND: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. OBJECTIVE: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. METHODS: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively. RESULTS: Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60±30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity. CONCLUSIONS: Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60±30-minutes time interval which requires further study. IOS Press 2018-07-30 /pmc/articles/PMC6087454/ /pubmed/30112440 http://dx.doi.org/10.3233/BLC-180166 Text en © 2018 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Karsh, Lawrence Shore, Neal Soloway, Mark Bhat, Gajanan Reddy, Guru Leu, Szu-Yun Witjes, J. Alfred Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title | Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title_full | Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title_fullStr | Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title_full_unstemmed | Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title_short | Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer |
title_sort | double-blind, randomized, placebo-controlled studies evaluating apaziquone (e09, qapzola™) intravesical instillation post transurethral resection of bladder tumors for the treatment of low-risk non-muscle invasive bladder cancer |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087454/ https://www.ncbi.nlm.nih.gov/pubmed/30112440 http://dx.doi.org/10.3233/BLC-180166 |
work_keys_str_mv | AT karshlawrence doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT shoreneal doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT solowaymark doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT bhatgajanan doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT reddyguru doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT leuszuyun doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer AT witjesjalfred doubleblindrandomizedplacebocontrolledstudiesevaluatingapaziquonee09qapzolaintravesicalinstillationposttransurethralresectionofbladdertumorsforthetreatmentoflowrisknonmuscleinvasivebladdercancer |