INITIAL REPORT ON INTRAVESICAL ADMINISTRATION OF N-TRIFLUOROACETYLADRIAMYCIN-14-VALERATE (AD-32) TO PATIENTS WITH REFRACTORY SUPERFICIAL TRANSITIONAL-CELL CARCINOMA OF THE URINARY-BLADDER

Objectives. This study was designed to assess the pharmacokinetics, sa fety, and antitumor activity of intravesically administered AD 32, a n ovel anthracycline, in patients with transitional cell carcinoma (TCC) of the bladder. Methods. Six weekly doses of AD 32 (200 to 900 mg) we re administered to 32 patients with superficial TCC who were candidate s for intravesical treatment. Serum drug levels were measured during t he 6-hour period after administration of the first, third, and sixth d oses. Patients underwent bladder evaluations at 3-month intervals to d etermine responses to treatment. Results. Very low levels of unmetabol ized AD 32 and its two primary metabolites were measured in serum. The lack of systemic exposure was confirmed by the finding of only a few minor systemic adverse events. Local bladder irritation, the main toxi city associated with intravesical administration of AD 32, persisted f or several days after each instillation. The maximum tolerated dose wa s 800 mg. Thirteen patients had complete responses to treatment, inclu ding 8 who remained disease free for 12.1 to 38.5 months. Conclusions. AD 32 is an active drug for the treatment of superficial bladder canc er, Further studies of intravesical administration of AD 32 are warran ted. (C) 1997, Elsevier Science Inc.