CHICAGODespite recent excitement about therapy involving
ifosfamide (Ifex) and other new chemotherapy drug combinations,
MVACmethotrexate, vinblastine, Adriamycin (doxorubicin), and
cisplatinremains the standard of care for advanced bladder
cancer, Derek Raghavan, MD, said at the Chicago Prostate Cancer
Shootout III Plus Bladder Conference, sponsored by the Chicago
Urological Society, Chicago Radiological Society, and Chicago Medical Society
Dr. Raghavan, chief of medical oncology, University of Southern
California Norris Cancer Center, acknowledged that some of the newer
drug combinations may be less toxic than MVAC, but they do not
significantly increase survival over that achieved with MVAC and may
produce significantly worse survival results.
MVAC has been considered the standard for treating advanced bladder
cancer since 1992 when it was tested against cisplatin in 600
patients and demonstrated a significant doubling in median survival.
However, the MVAC combination is extremely toxic and achieves a
median survival of only 12.5 to 13.4 months, Dr. Raghavan said.
Although replacing the highly toxic MVAC regimen with one that has
fewer severe adverse side effects is a laudable goal, he wondered,
Are these new combinations good enough in terms of survival?
In a phase II trial at Memorial Sloan-Kettering Cancer Center that
included many patients with lymph node metastases, the ITP
combination (ifosfamide, paclitaxel [Taxol], and platinum) yielded an
impressive median survival of 18 months.
Concerned that these results may represent stage migration, Dr.
Raghavan said that before we switch from MVAC to ITP, we should
be requiring that Sloan-Kettering or somebody else do the randomized
trial that asks the question: Is ITP better than MVAC? My hunch is
that ITP will be better, but not in terms of better survival; it will
just be less toxic. This is an important endpoint, but it is not the
same as saying ITP is a gigantic leap forward.
Results of a phase II trial of paclitaxel plus carboplatin, conducted
at Wayne State University, created enthusiasm because of its reduced
toxicity, but it is not a regimen I want to use routinely,
Dr. Raghavan said, because of its median survival of only 9.5
Use of Gemcitabine
The other new kid on the blockgemcitabine
(Gemzar)is an interesting drug for bladder cancer because of
early results from a 1997 clinical trial, Dr. Raghavan said. Median
survival was 14 months when gemcitabine was given with cisplatin in a
small multicenter study that included 47 patients with positive lymph
nodes and visceral disease.
Since then, he said, gemcitabine has been used in conjunction with
other chemotherapeutic agents in patients with metastatic bladder
When used with paclitaxel and carboplatin, gemcitabine had a high
response rate (17 of 29 patients had a partial response), but no
clear survival data have emerged from that trial. Gemcitabine is
being added to ITP along with doxorubicin in further tests at
Because gemcitabine by itself or in combination with other
chemotherapy agents is not as toxic as the MVAC regimen, it may prove
to be an effective treatment alternative. If survival data from
gemcitabine plus cisplatin are comparable to those with MVAC, then we
may have a new standard of care. If not, were back to square
one, Dr. Raghavan commented.