Intravesical gemcitabine in superficial bladder cancer: a phase II safety, efficacy and pharmacokinetic study

We investigated the safety, efficacy and pharmacokinetics of the intravesical administration of 2000 mg gemcitabine once a week in the four weeks before transurethral resection of superficial bladder cancer (TUR), and in the four successive weeks.

Nine patients with superficial transitional cell bladder carcinoma were studied. Two thousand mg of gemcitabine dissolved in 50 ml of distilled water were administered intravesically. The dwell time was 60 min. The pharmacokinetics of gemcitabine and its metabolite, 2',2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine before and after TUR. Cystoscopy was repeated 30 days after completion of the TUR treatment and subsequently at time intervals of one or two months.

No systemic toxicity was noted, and only three patients displayed modest signs of local toxicity. One patient had recurrence 1 month after TUR, three between 3 and 6 months, and another three after 8, 11 and 18 months, respectively; two were recurrence-free after 21 and 22 months, respectively. The peak plasma concentrations of gemcitabine never exceeded 1000 ng/ml before TUR and 350 ng/ml after TUR, and declined rapidly. The plasma levels of dFdU were higher than those of gemcitabine, increased until 60 min and then declined little. Between 52% and 100% of the gemcitabine dose was present in voided urine.

Intravesical gemcitabine, at the dose of 2000 mg, is well tolerated, is associated with minimal systemic absorption and has a moderate efficacy in the treatment of superficial bladder cancer.