Perioperative Chemotherapy for Patients With Locally Advanced Bladder Cancer
Status:
Active, not recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
Radical cystectomy remains the gold standard treatment for invasive non metastatic
transitional cell cancer (TCC) of the bladder. In contemporary series, specific survival
rates are about 60 to 65% at 5 years, decreasing for locally advanced disease to 45-50% in
patients with nonorgan-confined lymph-node negative tumours and to 30-35% in patients with
lymph node positive tumours. Perioperative chemotherapy (adjuvant ou neoadjuvant) has been
developed in order to improve these results. Thanks to randomized trials and meta-analysis,
it can be concluded that perioperative chemotherapy increases overall survival with an
absolute benefit of 5%, equating to a survival rate of 50% at 5 years for nonorgan-confined
tumours. However, the chemotherapy administration time and the optimal chemotherapy regimen
to be delivered are not yet determined. Meta-analyses have shown that the benefit is only
observed for chemotherapy regimens including cisplatin. In daily management 4 to 6 cycles of
gemcitabine and cisplatin are delivered since this combination has been shown to yield a
similar efficacy with a better tolerance as compared to the MVAC regimen (methotrexate,
vinblastine, doxorubicin and cisplatin) in the metastatic setting. As HD-MVAC has been shown
to be associated with higher response rates than MVAC in bladder metastatic disease, also a
better efficacy of HD-MVAC can be suspected in the perioperative setting. Investigators
therefore designed a randomized phase III study to compare the efficacy of GC and HD-MVAC in
term of progression-free survival in patients for whom chemotherapy has been decided, before
or after radical cystectomy. Secondary endpoints include overall survival, side effects,
response rate in the neoadjuvant setting and ancillary studies focusing on gemcitabine and
cisplatin sensitivity. The total number of patients projected is 500. The number of patients
is based on the median progression-free survival rate of 50% at 3 years observed in patients
treated with GC (standard arm A) in the perioperative setting. An absolute improvement of 10%
(HR=0.74) is expected with HD-MVAC (experimental arm B) with a=0.05 and b=0.20. An interim
analysis is planned after the occurrence of 174 events. With an estimated uniform accrual
rate of 140 patients per year for 3.5 years and exponential survival, the final analysis is
expected to occur 8 years after the start of the trial.