With its poor prognosis, ovarian cancer remains a disease in search
of definitive treatment. Although paclitaxel (Taxol) has improved the outlook,
advanced ovarian cancer still has a 5-year mortality rate of 65%. The real
problem, according to William P. McGuire III, md, clinical professor of
medicine at University of Mississippi School of Medicine, is the high rate
of relapse even after clinical remission.
Speaking at the 14th Chemotherapy Foundation Symposium, Dr. McGuire
said that paclitaxel in combination with cisplatin (Platinol) has shown
a 5-month improvement in progression-free survival and a 12- to 14-month
improvement in median survival over the previously standard treatment of
cisplatin and cyclophosphamide.
Nonetheless, he said, many patients fail to achieve a major response
to initial treatment, and among those who do, relapse is all too common.
Questions remain about the optimal dose, schedule, and duration of treatment
with paclitaxel, he added. In his opinion, cisplatin with a prior 24-hour
infusion of paclitaxel should be standard treatment.
The development of new drugs is confounded by the risk of development
of multidrug resistance, Dr. McGuire said. The taxanes are inducers of
the MDR gene in vitro, but the in vivo effect has not been established
in clinical trials. Docetaxel (Taxotere) has been shown to be active in
ovarian cancer, but problematic fluid retention, somewhat alleviated with
steroids, needs to be worked out, he said.
Among other drugs currently in trials, he mentioned gemcitabine (Gemzar),
which he said was easy to combine with other drugs, and had shown some
efficacy, though of short duration. Doxorubicin encapsulated in pegylated
liposomes (Doxil) may be useful in combination with cisplatin and paclitaxel,
as may oral etoposide (VePesid) and topotecan (Hycamtin).
When questioned about intraperitoneal chemotherapy, Dr. McGuire said
that it may be effective in patients with low-volume disease. He added
that pending results of new trials of intraperitoneal chemotherapy, this
approach may warrant reconsideration.