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 Treatment.
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(Drug information on doxorubicin) every 2 weeks (90 mg/m² for 3 doses), followed by biweekly paclitaxel (250 mg/m² for 3 doses), and, finally, biweekly cyclophosphamide(Drug information on 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 marrow transplant.