Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guérin therapy.
BACKGROUND
Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS).


METHODS
Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months.


RESULTS
Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed.


CONCLUSIONS
Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.
Bassi
P
P
Department of Urology, University of Padova Medical School, Padova, Italy. bassipf@tin.it
De Marco
V
V
Tavolini
I M
IM
Longo
F
F
Pinto
F
F
Zucchetti
M
M
Crucitta
E
E
Marini
L
L
Dal Moro
F
F
D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000627:therapeutic use; D000283:Administration, Intravesical; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001500:BCG Vaccine / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003558:Cystoscopy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D001500:BCG Vaccine; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; D000093542:Gemcitabine