PARIS--Physicians should strive to maintain intensive platinum
therapy in women with low-volume ovarian cancer, urged William
McGuire III, MD, of Emory University. "However, I don't think
there's yet data to show that we need to crank doses up to the
transplant level in order to improve the outcome," he said
at the Fifth International Congress on Anti-Cancer Chemotherapy.
Although high-dose chemotherapy is one of the few options open
to patients with recurrent ovarian cancer, the relationship between
dose intensity and outcome is not linear in the disease; doses
must be raised by as much as 10- to 100-fold to overcome intrinsic
Current Approaches Inadequate?
Dr. McGuire believes that current approaches to augmenting dose
intensity in ovarian cancer--autologous transplant and intraperitoneal
(IP) therapy--are probably inadequate to the task.
A just completed randomized trial comparing intraperitoneal versus
intravenous administration of platinum showed that IP therapy
offered an advantage in a very small subset of patients with low-volume
disease. "These results may make us all rethink the issue
of up-front intraperitoneal therapy," Dr. McGuire said. "As
a salvage therapy, we can get complete pathologic responses in
20% to 30% of patients, but how long the responses last is unknown."
While acknowledging that IP therapy offers some theoretical advantages,
he warned, "I don't think at this time that IP therapy should
be used in current practice outside the confines of well-designed
clinical trials." Dr. McGuire noted that the Gynecologic
Oncology Group (GOG) is now testing IP paclitaxel (Taxol) in a
phase II study.
The results of a randomized GOG trial of high-dose chemotherapy
in high-volume disease are likewise sobering. GOG investigators
found no difference in progression-free or overall survival between
women who had been assigned to four cycles of high-dose cyclophosphamide
(Cytoxan, Neosar) and platinum, and those who received eight cycles
of low-dose chemotherapy.