No / 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. 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. 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. Intravesical administration of 4 mg/40 ml apaziquone was well tolerated and had ablative activity against superficial bladder cancer marker lesions.

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An ultrasonic method to determine bladder volumes could help eliminate some of the risk and discomfort resulting from catheterizations. A system using "A" mode ultra-sound correctly estimates bladder volumes to within 50 cc's. Near and far walls of bladder sections found at various positions define the bladder, and volumes calculated from these sections are added together for a bladder volume estimate. Accurate volume estimates (mean error of -1.9 cc.'s with standard deviation of 28 cc.'s) were obtained when bladder section characteristics such as: depth of the near wall of the bladder, thickness of the far wall echo, distance between near and far bladder walls, and amplitude of the far bladder wall echo, were considered. Most bladders were completely scanned with the transducer placed at the bodies midline, approximately 5 to 7.5 cm. above the pubic bone.

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