RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining surgery with chemotherapy and radiation therapy may be an effective way to treat cancer of the urinary tract. PURPOSE: Phase II trial to study the effectiveness of combining surgery, chemotherapy and radiation therapy in treating patients who have stage II, stage III, or stage IV cancer of the urinary tract.

Condition	Treatment or Intervention	Phase
stage III bladder cancer stage II bladder cancer regional transitional cell cancer of the renal pelvis and ureter anterior urethral cancer stage IV bladder cancer urethral cancer associated with invasive bladder cancer metastatic transitional cell cancer of the renal pelvis and ureter posterior urethral cancer	Procedure: chemotherapy  Procedure: surgery  Procedure: radiation therapy  Procedure: conventional surgery  Drug: cisplatin  Drug: fluorouracil	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the quality of life of patients with invasive stage II, III, or IV carcinoma of the urothelium treated with conservative surgery plus cisplatin, fluorouracil, and radiotherapy. II. Determine the efficacy of this regimen, in terms of local control, in these patients. III. Determine survival of patients treated with this regimen. IV. Determine the toxic effects of this regimen in these patients.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (T2-4a, N0, M0; potentially resectable; no contraindication to surgery vs T2-4b, N0 or N1 or pN1, M0; refused surgery or medical contraindications to surgery). (Accrual for stratum I was completed as of 10/23/2001.) Stratum I (resectable disease): Regimen A: Patients undergo radiotherapy 5 days a week for 5 weeks. Patients also receive fluorouracil IV continuously and cisplatin IV continuously on days 1-4 during weeks 1 and 4. If complete response is achieved by week 5, patients proceed to regimen B. If partial response or progression is observed, patients undergo cystectomy. If cystectomy is refused, patients proceed to regimen B. Regimen B: Patients undergo radiotherapy 5 days a week for 2 weeks. Patients also receive fluorouracil and cisplatin as in regimen A on weeks 2 and 5. (Accrual for stratum I was completed as of 10/23/2001.) Stratum II (unresectable disease): Patients undergo radiotherapy 5 days a week for 7 weeks. Patients also receive fluorouracil and cisplatin as in regimen A on weeks 1, 4, and 7. Quality of life is assessed at baseline, at 6 months, and then at 1 year. Patients are followed at 6-8 weeks, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients (35 for stratum I and 40 for stratum II) will be accrued for this study. (Accrual for stratum I was completed as of 10/23/2001.)

Ages Eligible for Study:  18 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed stage II, III, or IV carcinoma of the urothelium infiltrating muscle; Primary OR After development of a superficial tumor; T2-T4b with or without lymph node involvement and no detectable metastases
• No epidermoid cancer or adenocarcinoma
• No extrapelvic lymph node involvement

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy except intravesicular instillations
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 to 70
• Performance status: WHO 0-2
• Life expectancy: More than 6 months
• Hematopoietic: WBC greater than 4,000/mm3; Platelet count greater than 100,000/mm3; Neutrophil count greater than 1,500/mm3; Hemoglobin greater than 10 g/dL
• Hepatic: Not specified
• Renal: Creatinine less than 1.5 mg/dL
• Other: Not pregnant; Fertile patients must use effective contraception during and for 2 months after study; No other prior malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix; No prior serious illness of the gastrointestinal tract (e.g., rectal bleeding or diverticulosis with complications); No contraindication to fluorouracil, cisplatin, or radiotherapy

France
      C.H.U. - Hopital Gaston Doumergue, Nimes,  30006,  France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre Eugene Marquis, Rennes,  35064,  France
      Centre Hospitalier General de Saint Nazaire, Saint-Nazaire,  44600,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Rene Huguenin, Saint Cloud,  92211,  France
      Institut Claudius Regaud, Toulouse,  31052,  France
      Institut Sainte Catherine, Avignon,  84082,  France

Study chairs or principal investigators

Jean-Leon Lagrange,  Study Chair,  Federation Nationale des Centres de Lutte Contre le Cancer   

Study ID Numbers:  CDR0000068123; FRE-FNCLCC-97015; EU-20009
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006111
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08