Try to Maintain Platinum Intensity in Low-Volume Ovarian Ca: McGuire

PARIS--Physicians should strive to maintain intensive platinumtherapy in women with low-volume ovarian cancer, urged WilliamMcGuire III, MD, of Emory University. "However, I don't thinkthere's yet data to show that we need to crank doses up to thetransplant level in order to improve the outcome," he saidat the Fifth International Congress on Anti-Cancer Chemotherapy.

Although high-dose chemotherapy is one of the few options opento patients with recurrent ovarian cancer, the relationship betweendose intensity and outcome is not linear in the disease; dosesmust be raised by as much as 10- to 100-fold to overcome intrinsicdrug resistance.

Current Approaches Inadequate?

Dr. McGuire believes that current approaches to augmenting doseintensity in ovarian cancer--autologous transplant and intraperitoneal(IP) therapy--are probably inadequate to the task.

A just completed randomized trial comparing intraperitoneal versusintravenous administration of platinum showed that IP therapyoffered an advantage in a very small subset of patients with low-volumedisease. "These results may make us all rethink the issueof up-front intraperitoneal therapy," Dr. McGuire said. "Asa salvage therapy, we can get complete pathologic responses in20% 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 shouldbe used in current practice outside the confines of well-designedclinical trials." Dr. McGuire noted that the GynecologicOncology Group (GOG) is now testing IP paclitaxel (Taxol) in aphase II study.

The results of a randomized GOG trial of high-dose chemotherapyin high-volume disease are likewise sobering. GOG investigatorsfound no difference in progression-free or overall survival betweenwomen who had been assigned to four cycles of high-dose cyclophosphamide(Cytoxan, Neosar) and platinum, and those who received eight cyclesof low-dose chemotherapy.

"So doubling the dose intensity in this population had nodiscernible effect on outcome," Dr. McGuire observed. Similarly,he pointed out, although an NCI trial revealed a higher responserate in patients who received high-dose paclitaxel than in thosewho received lower doses, this difference did not translate intoimproved survival.

Although autologous transplantation has been reported to permita twofold escalation of platinum dose, leading to an improvedresponse, it is still unknown whether further dose escalationwould yield an even better outcome, he said.

"It's clear that if we're going to do this, we should uselow-volume, drug-sensitive disease states, which can often beachieved only by the use of debulking surgery and low-dose inductionchemotherapy," he said.

Most Trials in Bulky Disease

But a series of US and European transplant trials were all smalland nonrandomized, and most were done in patients with bulky,often drug-resistant disease. Although response rates were 55%to 70% in these trials, the response duration was typically lessthan 6 months, he said.

Tackling the question of why high-dose breast cancer trials areyielding more optimistic results, Dr. McGuire pointed out thatbreast cancer trials are larger than ovarian cancer trials, aremore likely to include women with low-volume disease, and haverecently tended to focus on patients with disease that has notyet become resistant to therapy.