Phase I/II Pilot Study of Intravesical Apaziquone (EO9) for Superficial Bladder Cancer

Rajiv Puri, Victor Palit, Paul M. Loadman, Michael Flannigan, Tariq Shah, Guzanfar A. Choudry, Saurajyoti Basu, John A. Double, Gino Lenaz, Shanta Chawla, Mario Beer, Coen Van Kalken, Richard de Boer, Jos H. Beijnen, Christopher J. Twelves, Roger M. Phillips

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Purpose: The quinone based bioreductive drug apaziquone (EO9) failed to demonstrate efficacy in previous phase II studies following intravenous administration. We determined the dose of apaziquone that can be safely administered intravesically and explored its activity for superficial bladder transitional cell carcinoma. 

Materials and Methods: Six patients with multifocal, Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating doses of apaziquone formulated as EOquin™ (0.5 mg/40 ml up to 16 mg/40 ml) weekly for 6 weeks. A further 6 patients received weekly apaziquone at the highest nontoxic dose established. Pharmacokinetic parameters were determined in urine and blood, and the pharmacodynamic markers NQO1 (reduced nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase-1) and glucose transporter 1 were also characterized. Efficacy was determined against a marker lesion. 

Results: Local toxicity (grades 2 and 3 dysuria, and hematuria) was observed at doses of 8 mg/40 ml and above but 4 mg/40 ml was well tolerated with no systemic or local side effects. Apaziquone in urine increased linearly with the dose but no apaziquone was detected in plasma. In 8 of 12 patients complete macroscopic and histological disappearance of the marker lesion occurred. A correlation between response and NQO1 and/or glucose transporter 1 expression could not be established. 

Conclusions: Intravesical administration of 4 mg/40 ml apaziquone was well tolerated and had ablative activity against superficial bladder cancer marker lesions.

Original languageEnglish
Pages (from-to)1344-1348
Number of pages5
JournalJournal of Urology
Issue number4
Early online date3 Sep 2006
Publication statusPublished - Oct 2006
Externally publishedYes


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