Apaziquone (also known as EO9 and Qapzola) 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 minutes 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.
Expert opinion on drug metabolism & toxicology. 2017 Jun 21 [Epub ahead of print]
R M Phillips, H R Hendriks, J B Sweeney, G Reddy, G J Peters
a Department of Pharmacy , University of Huddersfield , Queensgate, Huddersfield HX1 3DH , United Kingdom., c Hendriks Pharmaceutical Consulting , Purmerend , The Netherlands., d Spectrum Pharmaceuticals Inc , 157 Technology Drive, Irvine , CA , 92618 , USA., e Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands .