Gemcitabine, Paclitaxel, and Cisplatin in Treating Patients With Advanced Cancer of the Urothelium

OBJECTIVES:

• Determine response to gemcitabine hydrochloride, paclitaxel, and cisplatin (GTP) among patients with regional or distant metastases of transitional cell carcinoma of the urothelium or local/regional recurrence after cystoprostatectomy.
• Determine response in patients who receive GTP as the initial chemotherapeutic treatment as well as in patients who have received prior chemotherapy.
• Determine response duration, freedom from progression, and overall survival.
• Assess the toxicity of GTP.

OUTLINE: This is an open-label study. Patients are stratified according to prior chemotherapy (yes vs no).

Patients receive paclitaxel IV over 3 hours and cisplatin IV over 1 hour on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving a partial response or complete response undergo surgical restaging and debulking. Four to 6 weeks later, patients receive 2 additional courses of chemotherapy.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma (TCC) of the urothelium (bladder, renal pelvis, or ureter) or TCC with squamous or glandular elements

• No pure squamous cell carcinoma or adenocarcinoma
• Disease not amenable to local curative treatment
• Regional or distant metastases of TCC of the urothelium OR local/regional recurrence after cystectomy, cystoprostatectomy, nephroureterectomy, or ureterectomy

• If regional metastases present alone, histological confirmation of the metastases is required
• No clinically evident brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0 or 1
• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Creatinine ≤ 1.6 mg/mL
• Bilirubin ≤ 1.8 mg/mL
• SGOT ≤ 3 times upper limit of normal
• Life expectancy > 3 months
• No known sensitivity to E. coli-derived products
• No other prior or concurrent malignancy except active/inactive nonmelanoma skin cancer, adequately treated stage I or II cancer currently in complete remission, or observation-only early-stage prostate cancer
• No other serious medical illness that would limit survival to < 3 months
• No psychiatric condition that would limit compliance with study requirements
• No active uncontrolled bacterial, viral, or fungal infection unless corrected or controlled
• No hemorrhagic disorder
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy regimen
• Prior intravesical therapy allowed
• Prior definitive radiation to renal pelvis, ureter, or bladder allowed
• No concurrent chemotherapy with nonstudy drugs