TY - JOUR

T1 - Efficacy, pharmacokinetic and pharmacodynamic evaluation of apaziquone in the treatment of non-muscle invasive bladder cancer

AU - Phillips, R. M.

AU - Hendriks, H. R.

AU - Sweeney, J. B.

AU - Reddy, G.

AU - Peters, G. J.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Apaziquone

KW - bioreductive prodrug

KW - EO9

KW - hypoxia activated prodrug

KW - NAD(P)H:quinone oxidoreductase 1 (NQO1)

KW - non-muscle invasive bladder cancer

KW - Qapzola

U2 - 10.1080/17425255.2017.1341490

DO - 10.1080/17425255.2017.1341490

M3 - Journal article

C2 - 28637373

AN - SCOPUS:85021800033

VL - 13

SP - 783

EP - 791

JO - Expert Opinion on Drug Metabolism and Toxicology

JF - Expert Opinion on Drug Metabolism and Toxicology

SN - 1742-5255

IS - 7

ER -