CHICAGOSystemic chemotherapy would seem to be a reasonable
option to reduce the number of deaths from metastatic transitional
cell bladder carcinoma. To date, however, systemic neoadjuvant
chemotherapy has failed to show an effect on survival, and the jury
is still out on the issue of chemotherapy following definitive
therapy, said Derek Raghavan, MD, chief of medical oncology,
University of Southern California Norris Cancer Center.
In the early 1980s, preliminary findings from trials of neoadjuvant
chemotherapy in patients with high-grade T3 and T4 transitional cell
carcinoma treated at the Royal Prince Alfred Hospital, Sydney,
Australia, suggested that two cycles of cisplatin before definitive
therapy might increase survival.
Follow-up randomized trials have not confirmed that neoadjuvant
chemotherapy confers a survival benefit, however, Dr. Raghavan said
at the Chicago Prostate Cancer Shootout III Plus Bladder Conference,
sponsored by the Chicago Urological Society, Chicago Radiological
Society, and Chicago Medical Society.
Early reporting from one of the best- designed randomized trials
conducted by EORTC in 1996 has shown no difference in survival when
CMV (cisplatin, methotrexate, vinblastine) was given before
definitive treatment for bladder cancer. The aim of the trial was to
try to detect a 10% increase in 3-year survival among 975 bladder
cancer patients treated in 16 countries, which is not asking
for too much, Dr. Raghavan said.
Nevertheless, there was no difference in any of the survival
measurements. Two-year disease-free survival was 51% in CMV-treated
patients and 45% in controls; overall 2-year survival was 62% in CMV
patients and 60% in controls.
These results are preliminary and, therefore, could change over time,
he noted. However, since the findings failed to show a survival
benefit at first analysis, we have no basis for using neoadjuvant
chemotherapy from this trial, Dr. Raghavan commented. The RTOG
trial of neoadjuvant CMV has provided another nail in the
coffin for neoadjuvant therapy, Dr. Raghavan said, because
there was no difference in actuarial 5-year survival (49% for
CMV-treated patients vs 48% for nontreated patients) and no
difference in overall 3-year survival.
Trials of adjuvant therapy after chemotherapy and surgery have
indicated that there may be at least some effect on survival;
however, many of these trials have been poorly designed, Dr. Raghavan
A study conducted by Freiha in 1996 demonstrated a trend toward
increased survival with adjuvant CMV after cystectomy, but it closed
early and therefore had too few cases to support the use of adjuvant
At present, therefore, Dr. Raghavan said, there is no routine
role for adjuvant chemotherapy other than in very carefully selected
patients or in the context of clinical trials.