A study published in the June 1, 1994 issue of the journal
Blood demonstrates that amifostine (Ethyol), a selective cytoprotective
agent, significantly shortens the time to bone marrow recovery
in breast cancer patients undergoing high-dose chemotherapy with
autologous bone marrow support. The study also found that amifostine
reduces the risk of blood-related complications and supportive
care requirements in these patients without reducing the chemotherapy's
effectiveness against tumors.
"We were impressed with amifostine's unique ability to selectively
protect a broad range of normal tissue including bone marrow,
but not tumors, from damage," says Elizabeth J. Shpall, MD,
associate director, University of Colorado Bone Marrow Transplant
Program, and lead author of the study. "This study demonstrates
that amifostine protection significantly shortens the time to
bone marrow recovery."
High-dose chemotherapy with autologous bone marrow support, or
ABMS, is often effective in treating patients with high-risk breast
cancer. Purging the marrow with chemotherapeutic drugs such as
4-hydroperoxycyclophosphamide (4-HC) effectively kills tumor cells,
but also is toxic to normal marrow and can delay the ability of
the healthy marrow to form new blood cells. This increases the
risk of complications such as fever and infection due to low white
blood cell count, and can increase the cost of supportive therapy
(such as blood transfusions and antibiotic treatment).
The University of Colorado Bone Marrow Transplant Program study
was designed to determine if amifostine administered prior to
bone marrow purging could reduce the toxicity to normal marrows
cells without reducing the effectiveness of 4-HC against tumor
Bone marrow was removed from 15 breast cancer patients, who were
assigned to treatment with amifostine and 4-HC, or treatment with
4-HC alone, followed by high-dose chemotherapy with cyclophosphamide,
cis-platin and carmustine.
The researchers found that marrow that was treated with amifostine
prior to purging with 4-HC resulted in a 200-fold higher recovery
of cells that produce white blood cells compared with marrow treated
with 4-HC alone, with no reduction in the antitumor effect. The
researchers also report:
Marrow engraftment was achieved in an average of 26 days with
amifostine treatment compared with an average of 36 days for patients
whose marrow was treated with 4-HC alone.
The average number of blood platelet transfusions was significantly
less for patients with amifostine-treated marrow compared with
those purged with 4-HC alone (12 transfusions vs 29 transfusions).
Patients whose marrow was pretreated with amifostine received
fewer days of antibiotic therapy than patients whose marrow was
treated with 4-HC alone (28 days vs 40 days).
Three patients whose marrow was purged with 4-HC along required
infusions of untreated reserve marrow to recover, while none of
the patients whose marrow was exposed to amifostine needed such
"The results of this study offer significant implications
in terms of reducing blood-related complications and toxicities
associated with bone marrow support and opening the door for more
effective therapies," adds Dr. Shpall. "Additionally,
since supportive care needs for patients with infections and bleeding
are major contributors to the cost of bone marrow therapy, this
study suggests a strong likelihood that amifostine can reduce
the expense of treatment for patients who receive 4-HC-purged
autologous bone marrow support."
The research was conducted by the University of Colorado Bone
Marrow Transplant Program with grant support from U.S. Bioscience,
maker of amifostine.