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Sequential High Dose Chemotherapy for Breast Cancer
Linda T. Vahdat
Department of Medicine, Division of Medical Oncology, Columbia University
College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer
Center, New York, NY
While breast cancer is considered a highly curable disease if detected early in
its course, the disseminated disease imparts a grave prognosis with a median
survival of less than 3 years. 1,2
High-dose chemotherapy increases the number of
patients achieving a complete response (CR) to cytotoxic chemotherapy when
compared with conventional dose chemotherapy; however, it does not appear that
this increased response rate has reliably translated into a similarly increased
disease-free survival rate. 3
There are several published series of sequential highdose
chemotherapy regimens in breast cancer. 4-6
Early clinical trials of sequential
high-dose chemotherapy were hampered by high morbidity and mortality rates due
to the sole use of bone marrow as a stem cell source and lack of hematopoietic
growth factors. The use of peripheral blood progenitors and growth factors hastens
blood count recovery and has significantly lowered the morbidity and mortality of
this approach.
Many strategies have been employed to increase the complete response rate,
including the incorporation of new drugs or schedules into established
chemotherapy treatment regimens. Other approaches include novel posttransplant
consolidation strategies with various types of immune modulation. 7-16
There are
several arguments in favor of sequential high-dose chemotherapy as opposed to a
single high-dose cycle. Most important among them, according to registry data, is
that a CR to therapy is considered the most important prognostic factor associated
with a prolonged disease-free survival. Hence, if multiple cycles can increase the
CR rate, then perhaps this may translate into prolonged disease-free survival.
Several trials of sequential high-dose chemotherapy have been completed over the
past 8 years. A recent compilation revealed that the CR rate ranged from 23 to 93%
with as many as 35% disease free at 44 months of follow-up. 17
Paclitaxel is one of the most exciting drugs to emerge in the last 20 years and
has been incorporated into transplant regimens by many other investigators.
Response rates vary, with some reported as high as 93%. 18
The group at Columbia
has piloted a regimen that incorporated paclitaxel at doses ranging from 400 to 825
mg/m 2
as the first of three separate high-dose cycles of chemotherapy supported
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