4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: cisplatin; doxorubicin hydrochloride; methotrexate; vinblastine
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 521.0
Sex: All
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I bladder cancer; stage II bladder cancer; transitional cell carcinoma of the bladder

Summary:

      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining more than one drug may kill more tumor cells. It is not
      yet known whether combination chemotherapy is more effective than observation alone in
      treating bladder cancer.

      PURPOSE: This randomized phase III trial is studying combination chemotherapy to see how well
      it works compared to observation alone in treating patients with bladder cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically proven organ confined transitional cell carcinoma (TCC) of the bladder

               -  Must have undergone radical cystectomy and bilateral pelvic lymphadenectomy with
                  pathologic stage from definitive cystectomy specimen of P1, P2a, or P2b and N0,
                  M0 TCC with or without squamous/glandular differentiation (no adenocarcinoma,
                  squamous cell carcinoma, or small cell carcinoma)

                    -  Margins must be negative for invasive or in situ TCC

                    -  In situ TCC in the urethra or ureter(s) allowed provided margins are
                       negative

               -  Clinical stage T1, T2a, or T2b based on transurethral resection bladder tumor
                  specimen with P0 or PIS and N0, M0 TCC allowed

               -  Incidental pT2a (Gleason score no greater than 7), pT2b (Gleason score no greater
                  than 7), or pT2c (Gleason score no greater than 7) adenocarcinoma of the prostate
                  allowed

          -  No invasive tumor into ureter(s) or urethra

          -  Must have potentially curable disease

          -  Must register within 9 weeks after surgery

          -  No metastatic disease by physical exam and chest x-ray or CT scan of the chest

          -  Eligible for randomization if:

               -  p53 gene alteration present

               -  Randomization occurs within 10 weeks after surgery

               -  Those who are randomized to receive (MVAC) methotrexate, vinblastine,
                  doxorubicin, and cisplatin begin MVAC within 12 weeks after cystectomy

               -  No metastatic disease by physical exam and chest x-ray or CT scan of the chest

               -  No prohibitive medical risk for chemotherapy

        PATIENT CHARACTERISTICS:

        Age

          -  Any age

        Performance status

          -  ECOG 0-1 OR

          -  Karnofsky 70-100%

        Life expectancy

          -  Not specified

        Hematopoietic

          -  WBC at least 4,000/mm^3

          -  Platelet count at least 150,000/mm^3

        Hepatic

          -  SGOT or SGPT no greater than 2 times normal

          -  Alkaline phosphatase no greater than 2 times normal

          -  Bilirubin normal

        Renal

          -  Creatinine no greater than 1.8 mg/dL OR

          -  Creatinine clearance at least 50 mL/min

          -  Blood urea nitrogen normal

        Cardiovascular

          -  No serious arrhythmias

          -  No congestive heart disease with New York Heart Association class III or IV status

          -  Randomization group:

               -  Ejection fraction must be at least 50% by MUGA scan if there is a clinical
                  concern regarding the patient's cardiac status

        Other

          -  No other malignancy (including synchronous papillary or invasive upper urinary tract
             malignancy) within the past 5 years except incidental prostate cancer (found at
             cystectomy), basal cell or squamous cell skin cancer, or carcinoma in situ of the
             cervix

          -  No concurrent advanced medical illness or psychologic disease

          -  No prohibitive medical risk for chemotherapy

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  Not specified

        Chemotherapy

          -  See Disease Characteristics

          -  No prior systemic chemotherapy for bladder cancer

          -  At least 5 years since other prior systemic chemotherapy

          -  Prior intravesical therapy allowed

          -  Randomization group:

               -  Prior intravesical therapy allowed if administered prior to cystectomy

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  No prior pelvic irradiation

        Surgery

          -  See Disease Characteristics