Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer

OBJECTIVES:

- Evaluate the safety and tolerability of induction chemoradiotherapy with paclitaxel and
cisplatin followed by selective bladder preservation or radical cystectomy and adjuvant
chemotherapy in patients with stage II or III muscle invasive carcinoma of the bladder
previously treated with transurethral tumor resection.

- Evaluate the efficacy of transurethral tumor resection and induction chemoradiotherapy
in achieving a complete response in this patient population.

- Assess the value of tumor parameters as prognostic factors for initial tumor response
and recurrence-free survival in this patient population.

OUTLINE: Four to six weeks after prior transurethral resection, patients receive induction
therapy comprising paclitaxel IV over 1 hour on days 1, 8, and 15, cisplatin IV over 1 hour
on days 1, 2, 8, 9, 15, and 16, and radiotherapy twice daily on days 1-5, 8-12, and 17.

Four weeks after induction therapy, patients undergo urologic evaluation. At 1-2 weeks after
evaluation, patients with complete response receive consolidation therapy comprising
paclitaxel IV over 1 hour on days 1 and 8, cisplatin IV over 1 hour on days 1, 2, 8, and 9,
and radiotherapy twice daily on days 1-5 and 8-10. Patients with poor tumor response undergo
a cystectomy.

At 12 weeks postconsolidation therapy or 8 weeks post radical cystectomy, patients receive
adjuvant chemotherapy comprising gemcitabine IV over 30-60 minutes followed by cisplatin IV
over 1 hour every 3 weeks. Treatment repeats every 4 weeks for 4 courses in the absence of
disease progression or unacceptable toxicity.

Patients are followed every 4 months for 1 year, every 6 months for 3 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed stage II or III (T2-4a, Nx or N0, M0) primary carcinoma of
the bladder with muscle invasion

- Resectable disease

- Prostatic urethral involvement with transitional cell carcinoma allowed, if
completely resected and no evidence of stromal invasion

- No tumor-related hydronephrosis

- Positive lymph node must be evaluated by lymphadenectomy or percutaneous needle
biopsy

- No nodal metastases

- No distant metastases

- No more than 6 weeks since prior transurethral resection of the bladder tumor

- Functioning bladder

PATIENT CHARACTERISTICS:

Age:

- Adult

Performance status:

- Zubrod 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Hemoglobin at least 10 g/dL

- White blood cell (WBC) count of at least 4,000/mm^3

- Absolute neutrophil count at least 1,800/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

Renal:

- Creatinine no greater than 1.5 mg/dL

- Creatinine clearance at least 60 mL/min

Other:

- No other prior or concurrent malignancy within the past 5 years except curatively
treated nonmelanoma skin cancer, stage I prostate cancer, or carcinoma in situ of the
cervix

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- Medically operable

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior systemic chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior pelvic radiotherapy

Surgery:

- See Disease Characteristics

Other:

- No concurrent potential nephrotoxic or ototoxic drugs (e.g., aminoglycosides)