S0121, Neoadjuvant Carboplatin, Paclitaxel, and Gemcitabine Followed by Cisplatin and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Carcinoma of the Urothelium

OBJECTIVES:

• Determine the overall survival of patients with locally advanced or recurrent carcinoma of the urothelium treated with neoadjuvant carboplatin, paclitaxel, and gemcitabine followed by concurrent cisplatin and radiotherapy.
• Determine the feasibility of administering this regimen to these patients.
• Determine the progression-free survival of patients treated with this regimen.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Determine the response rate (confirmed and unconfirmed) of patients treated with the neoadjuvant regimen and those treated with the whole regimen.
• Determine the proportion of patients who qualify for concurrent cisplatin and radiotherapy after receiving the neoadjuvant regimen.
• Determine the potential value of suppressor gene expression analysis (p53 and retinoblastoma gene) and HER2 expression as indicators of prognosis and/or response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after the completion of neoadjuvant chemotherapy, patients receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for a maximum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary or recurrent invasive carcinoma of the urothelium

• Transitional, squamous, or mixed cell subtypes allowed
• Primary disease site must be the urinary bladder or urethra
• Disease confined to the true pelvis (T2-T4, N0-N3, M0)
• Must meet at least 1 of the following criteria:

• Nodal involvement at or below the level of the bifurcation of the iliac vessels
• Medically or surgically inoperable
• Patient refused cystectomy
• Measurable or nonmeasurable disease
• Evidence of tumor invasion of the muscularis by cystoscopy and biopsy and detailed bladder mapping within the past 56 days
• No extrapelvic metastases
• Eligible to receive radiotherapy

• Planned radiotherapy at a SWOG-approved facility

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least lower limit of normal

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT or SGPT no greater than 2.5 times ULN

Renal

• Creatinine clearance at least 60 mL/min OR
• Creatinine no greater than ULN

Gastrointestinal

• No chronic diarrhea
• No malabsorption
• No extensive diverticular disease of the colon
• No inflammatory bowel disease
• No other pre-existing gastrointestinal disorders

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No active infections requiring antibiotics
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for patients with a current diagnosis of advanced bladder cancer that is also the initial diagnosis
• No prior systemic chemotherapy except adjuvant therapy for recurrent disease completed more than 6 months ago
• No prior carboplatin
• No prior paclitaxel
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior pelvic radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery