Intravesical drug delivery. Pharmacokinetic and clinical considerations.
Intravesical drug administration is widely used in the treatment of patients with superficial bladder cancer, and aims to optimise drug delivery in the vicinity of the tumour and reduce systemic availability. The most commonly employed intravesical agents in patients with superficial bladder cancer are mitomycin (mitomycin C), thiotepa, ethoglucid (ethoglucid), anthracyclines such as doxorubicin, bacille Calmette-Guérin (BCG) and, more recently, taxol and the new mitomycin derivative KW-2149. Recurrence rates in patients with superficial bladder cancer have been substantially reduced by combined transurethral resection and intravesical pharmacotherapy. The high concentration of cytotoxics in urine and tumour tissue explain the high efficacy rates. Furthermore, the low systemic availability of most intravesical agents is consistent with the low frequency of acute and delayed systemic adverse effects. Systemic toxicity is almost negligible, except in the case of thiotepa, and local toxicity is transient and tolerable. Pharmacokinetic models of drug absorption from the bladder have been developed, both in animals and humans. These have led to the identification of optimal intravesical treatment regimens.
Highley
M S
MS
Northern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle upon Tyne, England.
van Oosterom
A T
AT
Maes
R A
RA
De Bruijn
E A
EA
D000042:Absorption; D000283:Administration, Intravesical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage / Q000627:therapeutic use; D008954:Models, Biological; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin