Efficacy, Pharmacokinetic and Pharmacodynamic Evaluation of Apaziquone in the Treatment of non-Muscle Invasive Bladder Cancer

R. M. Phillips, H. R. Hendriks, J. B. Sweeney, G. Reddy, G. J. Peters

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction: Apaziquone (also known as EO9 and QapzolaTM) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. 

Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 min or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. 

Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers.

LanguageEnglish
Pages783-791
Number of pages9
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume13
Issue number7
Early online date3 Jul 2017
DOIs
Publication statusPublished - 2017

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apaziquone
Pharmacodynamics
Pharmacokinetics
Urinary Bladder Neoplasms
Therapeutics
Phase III Clinical Trials
Phase II Clinical Trials
Prodrugs
Expert Testimony
Biomarkers
Surgery
Neoplasms

Cite this

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abstract = "Introduction: Apaziquone (also known as EO9 and QapzolaTM) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 min or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers.",
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Efficacy, Pharmacokinetic and Pharmacodynamic Evaluation of Apaziquone in the Treatment of non-Muscle Invasive Bladder Cancer. / Phillips, R. M.; Hendriks, H. R.; Sweeney, J. B.; Reddy, G.; Peters, G. J.

In: Expert Opinion on Drug Metabolism and Toxicology, Vol. 13, No. 7, 2017, p. 783-791.

Research output: Contribution to journalArticle

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