PARIS--Although properly applied high-dose chemotherapy can produce
massive cytoreduction in breast cancer, it may not be adequate
to cure the disease. "The problem has never been the achievement
of remissions with high-dose therapy; the problem is making them
stick," Larry Norton, MD, of Memorial Sloan-Kettering Cancer
Center, said at the Sixth International Congress on Anti-Cancer
A more promising strategy for disease eradication, he said, may
be dose-dense sequential chemotherapy, possibly in conjunction
with antibodies that target the growth factor receptor HER2.
Dr. Norton believes that cell kill is more rigorously accomplished
by administering chemotherapy more frequently than by simply increasing
the dose. The traditional simultaneous or alternating use of chemotherapeutic
agents does not increase dose density, he said.
To maximize cell kill and avert regrowth, he advised oncologists
to give all of one agent first with very short intervals between
doses, and then follow with a second and third agent.
"After many years, we evolved an outpatient adjuvant regimen
that is not as toxic as others and does not require stem cell
support," Dr. Norton said. With this regimen, the use of
G-CSF is adequate to allow administration of doxorubicin every
2 weeks (90 mg/m² for 3 doses), followed by biweekly paclitaxel
(250 mg/m² for 3 doses), and, finally, biweekly cyclophosphamide
(3 g/m² for 3 doses).
"This regimen has been piloted in over 100 women with stage
II disease and four or more positive lymph nodes, and accomplishes
a 90% disease-free survival rate at 2 years in patients with a
median of nine positive nodes," Dr. Norton said.
The American Intergroup is now planning a randomized study for
women with four to nine positive nodes that will compare this
regimen with high-dose combination chemotherapy supported by bone