title: Phase I/II pilot study of intravesical apaziquone (EO9) for superficial bladder cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Six patients with multifocal, Ta/T1 and G1/G2 transitional cell carcinoma of the bladder received escalating doses of apaziquone formulated as EOquintrade mark (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.
authors.affiliation: Department of Urology, Bradford Royal Infirmary, Bradford, United Kingdom.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Puri
authors.forename: Victor
authors.initials: V
authors.lastname: Palit
authors.forename: Paul M
authors.initials: PM
authors.lastname: Loadman
authors.forename: Michael
authors.initials: M
authors.lastname: Flannigan
authors.forename: Tariq
authors.initials: T
authors.lastname: Shah
authors.forename: Guzanfar A
authors.initials: GA
authors.lastname: Choudry
authors.forename: Saurajyoti
authors.initials: S
authors.lastname: Basu
authors.forename: John A
authors.initials: JA
authors.lastname: Double
authors.forename: Gino
authors.initials: G
authors.lastname: Lenaz
authors.forename: Shanta
authors.initials: S
authors.lastname: Chawla
authors.forename: Mario
authors.initials: M
authors.lastname: Beer
authors.forename: Coen
authors.initials: C
authors.lastname: Van Kalken
authors.forename: Richard
authors.initials: R
authors.lastname: de Boer
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: Roger M
authors.initials: RM
authors.lastname: Phillips
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001388:Aziridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D045563:Indolequinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; C060817:apaziquone