Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant
therapy. Early results of administration of high-dose
chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary
breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary
breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III
breast cancer and 4-9 involved axillary lymph nodes received
doxorubicin-based
induction chemotherapy, followed by high-dose
cyclophosphamide (5.625 g/m2),
cisplatin (165 mg/m2), and
BCNU (450 mg/m2) and PBPC mobilized by
sargramostim (
GM-CSF) or
filgrastim (
G-CSF). After completion of HDCT, patients received
radiation therapy to the chest wall or involved breast, plus
tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of
BCNU were determined and plasma AUC(
BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary
drug toxicity, which resolved with a 10-week course of
corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of
induction chemotherapy, seven of whom have died. Forty-three patients are alive and
breast cancer-free at a median of 947 days (range 661-1730 days) after the start of
therapy, including one patient who developed
myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(
BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of
BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary
breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.