title: Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma.
abstract: Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, non-randomized dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10-150 mg ml(-1) in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml(-1). Urinary VEGF was affected by Suramin at doses above 50 mg ml(-1), corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml(-1) intravesically.
authors.affiliation: Department of Urology, Churchill Hospital, Oxford, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Ord
authors.forename: E
authors.initials: E
authors.lastname: Streeter
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: K
authors.initials: K
authors.lastname: Le Monnier
authors.forename: D
authors.initials: D
authors.lastname: Cranston
authors.forename: J
authors.initials: J
authors.lastname: Crew
authors.forename: S P
authors.initials: SP
authors.lastname: Joel
authors.forename: M A
authors.initials: MA
authors.lastname: Rogers
authors.forename: R E
authors.initials: RE
authors.lastname: Banks
authors.forename: I S D
authors.initials: IS
authors.lastname: Roberts
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011507:Proteinuria; D013498:Suramin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D013498:Suramin