Efficacy, pharmacokinetic and pharmacodynamic evaluation of apaziquone in the treatment of non-muscle invasive bladder cancer

ABSTRACT

Introduction: Apaziquone (also known as EO9 and Qapzola^TM) 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.

KEYWORDS:

• Apaziquone
• Qapzola^TM
• bioreductive prodrug
• EO9
• hypoxia activated prodrug
• NAD(P)H:quinone oxidoreductase 1 (NQO1)
• non-muscle invasive bladder cancer

Acknowledgement

This paper was written in the framework of the EORTC Pharmacology and Molecular Mechanism (PAMM) Group.

Declaration of interest

GJ Peters has received research funding from Spectrum pharmaceuticals, but not for apaziquone, HR Hendriks is the owner of Hendriks consulting. G Reddy is an employee and shareholder of Spectrum pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

Funding

This paper was not funded.