| Abstract: |
Purpose: 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. Patients and 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). Conclusion: 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. © 2002 by American Society of Clinical Oncology. |
| Keywords: |
adult; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; clinical trial; neutropenia; doxorubicin; dose response; drug safety; skin manifestation; gemcitabine; cytology; bcg vaccine; controlled clinical trial; antimetabolites, antineoplastic; thrombocytopenia; dose-response relationship, drug; urinary bladder neoplasms; hematuria; thiotepa; drug blood level; phase 1 clinical trial; carcinoma, transitional cell; administration, intravesical; mitomycin; bladder carcinoma; hand foot syndrome; deoxycytidine; transitional cell carcinoma; sodium chloride; valrubicin; illness behavior; superficial cancer; humans; human; male; female; priority journal; article; bladder irritation
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