Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.

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.

• Authors: Guido Dalbagni, Paul Russo, Joel Sheinfeld, Madhu Mazumdar, William Tong, Farhang Rabbani, Machelle S Donat, Harry W Herr, Pramod Sogani, Dominique dePalma, Dean Bajorin
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 20 Issue 15 Pg. 3193-8 (Aug 01 2002) ISSN: 0732-183X [Print] United States
• PMID: 12149290 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• BCG Vaccine
• Deoxycytidine
• Gemcitabine

Topics

• Administration, Intravesical
• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects)
• BCG Vaccine (administration & dosage)
• Carcinoma, Transitional Cell (drug therapy, pathology)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Treatment Outcome
• Urinary Bladder Neoplasms (drug therapy, pathology)
• Gemcitabine