Amifostine Shortens Bone Marrow Recovery Period in Breast Cancer Patients

A study published in the June 1, 1994 issue of the journalBlood demonstrates that amifostine (Ethyol), a selective cytoprotectiveagent, significantly shortens the time to bone marrow recoveryin breast cancer patients undergoing high-dose chemotherapy withautologous bone marrow support. The study also found that amifostinereduces the risk of blood-related complications and supportivecare requirements in these patients without reducing the chemotherapy'seffectiveness against tumors.

"We were impressed with amifostine's unique ability to selectivelyprotect 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 TransplantProgram, and lead author of the study. "This study demonstratesthat amifostine protection significantly shortens the time tobone marrow recovery."

High-dose chemotherapy with autologous bone marrow support, orABMS, is often effective in treating patients with high-risk breastcancer. Purging the marrow with chemotherapeutic drugs such as4-hydroperoxycyclophosphamide (4-HC) effectively kills tumor cells,but also is toxic to normal marrow and can delay the ability ofthe healthy marrow to form new blood cells. This increases therisk of complications such as fever and infection due to low whiteblood 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 studywas designed to determine if amifostine administered prior tobone marrow purging could reduce the toxicity to normal marrowscells without reducing the effectiveness of 4-HC against tumorcells.

Bone marrow was removed from 15 breast cancer patients, who wereassigned to treatment with amifostine and 4-HC, or treatment with4-HC alone, followed by high-dose chemotherapy with cyclophosphamide,cis-platin and carmustine.

The researchers found that marrow that was treated with amifostineprior to purging with 4-HC resulted in a 200-fold higher recoveryof cells that produce white blood cells compared with marrow treatedwith 4-HC alone, with no reduction in the antitumor effect. Theresearchers also report:

Marrow engraftment was achieved in an average of 26 days withamifostine treatment compared with an average of 36 days for patientswhose marrow was treated with 4-HC alone.

The average number of blood platelet transfusions was significantlyless for patients with amifostine-treated marrow compared withthose purged with 4-HC alone (12 transfusions vs 29 transfusions).

Patients whose marrow was pretreated with amifostine receivedfewer days of antibiotic therapy than patients whose marrow wastreated with 4-HC alone (28 days vs 40 days).

Three patients whose marrow was purged with 4-HC along requiredinfusions of untreated reserve marrow to recover, while none ofthe patients whose marrow was exposed to amifostine needed suchtreatment.

"The results of this study offer significant implicationsin terms of reducing blood-related complications and toxicitiesassociated with bone marrow support and opening the door for moreeffective therapies," adds Dr. Shpall. "Additionally,since supportive care needs for patients with infections and bleedingare major contributors to the cost of bone marrow therapy, thisstudy suggests a strong likelihood that amifostine can reducethe expense of treatment for patients who receive 4-HC-purgedautologous bone marrow support."

The research was conducted by the University of Colorado BoneMarrow Transplant Program with grant support from U.S. Bioscience,maker of amifostine.