Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery

• Rate of distant metastasis at 3 years [ Designated as safety issue: No ]
  

• Treatment completion rate [ Designated as safety issue: No ]
  
• Grade 3 or more genitourinary, gastrointestinal, and hematologic toxicities as assessed by NCI CTCAE v4.0 [ Designated as safety issue: Yes ]
  
• Complete response of the primary tumor [ Designated as safety issue: No ]
  
• Preservation of the native, tumor-free bladder 5 years after completion of study therapy [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin.

Secondary

• To estimate the treatment completion rate in these patients.
• To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients.
• To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients.
• To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients.
• To estimate the value of tumor histopathologic, molecular genetic, DNA content, metabolomic, and proteomic parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival.
• To analyze for AUA Symptom scores at baseline and at 3 years from patients on both arms.
• To find potentially predictive biomarkers for cystectomy-free survival.
• To find potentially predictive biomarkers for acute and late toxicities.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.

• Induction therapy (weeks 1-4):

  • Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 15-17 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also undergo radiotherapy twice daily on days 1-5, 8-12, and 15-17.
  • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, 15, 18, 22, and 25. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, and 22-26.

All patients undergo evaluation of response at 3-4 weeks after completion of induction therapy. Patients with pT1 or worse tumor response undergo radical cystectomy within 3-8 weeks after response evaluation. Patients with pT0, Ta, or Tis tumor response (at site distant from original tumor) proceed to consolidation therapy within 7-14 days after response evaluation.

• Consolidation therapy (weeks 8-10):

  • Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 8-10 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also undergo radiotherapy twice daily on days 1-5 and 8-10.
  • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, and 15. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15, and 16.

Patients proceed to adjuvant therapy 12 weeks after completion of consolidation therapy OR 8-12 weeks after radical cystectomy.

• Adjuvant therapy (weeks 21-33 or 17-29): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.