Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.
OBJECTIVE
The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder.


METHODS
Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg.


RESULTS
Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology).


CONCLUSIONS
Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.
Dalbagni
Guido
G
Department of Urology, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. dalbagng@mskcc.org
Russo
Paul
P
Sheinfeld
Joel
J
Mazumdar
Madhu
M
Tong
William
W
Rabbani
Farhang
F
Donat
Machelle S
MS
Herr
Harry W
HW
Sogani
Pramod
P
dePalma
Dominique
D
Bajorin
Dean
D
D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001500:BCG Vaccine / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D001500:BCG Vaccine; D003841:Deoxycytidine; D000093542:Gemcitabine