Trial Information

A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy

OBJECTIVES:

- Estimate the safety and tolerability of induction paclitaxel, cisplatin, and
radiotherapy or fluorouracil, cisplatin, and radiotherapy followed by consolidation
chemoradiotherapy or radical cystectomy and adjuvant gemcitabine, paclitaxel, and
cisplatin in patients with operable stage II or III bladder cancer.

- Estimate the efficacy of these regimens, in terms of complete response, in patients who
have undergone prior transurethral resection (TUR).

- Estimate the efficacy of these regimens after TUR, in terms of preserving the native
tumor-free bladder 5 years after therapy, in these patients.

- Estimate the function of the preserved bladder in patients treated with these regimens
after TUR.

- Determine the value of tumor histopathologic, molecular genetic, and DNA content
parameters as possible prognostic factors for initial tumor response and
recurrence-free survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T
stage (T2 vs T3/T4 ). Patients are randomized to one of two treatment arms.

- Induction therapy (weeks 1-3):

- Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and
cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also receive
pelvic radiotherapy twice daily on days 1-5, 8-12, and 15-17.

- Arm II: Patients receive fluorouracil IV over 24 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 receive
pelvic radiotherapy as in arm I.

Patients in both arms who achieve complete response after induction therapy proceed to
consolidation therapy on week 8. Patients with operable pT1 or worse tumor response proceed
to radical cystectomy on week 9.

- Consolidation therapy (weeks 8 and 9):

- Arm I: Patients receive paclitaxel IV over 1 hour on days 1 and 8 and cisplatin IV
over 1 hour on days 1, 2, 8, and 9. Patients also receive pelvic radiotherapy
twice daily for 8 days.

- Arm II: Patients receive 5-FU IV over 24 hours on days 1-3 and 8-10 and cisplatin
as in arm I. Patients also receive radiotherapy as in arm I.

- Adjuvant chemotherapy (weeks 21-33 or 17-29): Beginning 12 weeks after consolidation
therapy or 8 weeks after radical cystectomy, patients receive gemcitabine IV over 30-60
minutes, paclitaxel IV over 1 hour, and cisplatin IV over 1 hour on days 1 and 8.
Treatment repeats every 3 weeks for 4 courses.

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.

PROJECTED ACCRUAL: A total of 96 patients (48 per treatment arm) will be accrued for this
study within 3 years.