HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS PERIPHERAL-BLOOD PROGENITOR-CELL SUPPORT FOR PRIMARY BREAST-CANCER IN PATIENTS WITH 4-9 INVOLVED AXILLARY LYMPH-NODES

Breast cancer patients with more than three involved axillary lymph ha ve a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peri pheral blood progenitor cells (PBPC) to patients with primary breast c ancer and greater than or equal to 10 involved axillary nodes have bee n encouraging. We performed a multicenter trial to determine whether H DCT could be safely administered to patients with primary breast cance r involving 4-9 axillary lymph nodes. Fifty-four patients with stage I I or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclop hosphamide (5.625 g/m(2)), cisplatin (165 mg/m(2)), and BCNU (450 mg/m (2)) 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-f ree survival, time to engraftment, and charges associated with HDCT we re determined. Plasma concentrations of BCNU were determined and plasm a AUC(BCNU) was calculated. Fifty-four patients were evaluable for sur vival 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 subsequ ently died of pulmonary toxicity. Ten patients relapsed a median of 42 6 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast ca ncer-free at a median of 947 days (range 661-1730 days) after the star t of therapy, including one patient who developed myelodysplastic synd rome 809 days after the start of HDCT. Actuarial 4-year survival and d isease-free survival from the start of treatment are 84 and 71%, respe ctively. Mean plasma AUC(BCNU) was 400 (range 82-1255) mu g.min/ml and was not statistically different from that measured in historical cont rols who received 600 mg/m(2) of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125 845 for the first four patients to $77 126 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 ra ndomized trial is evaluating the efficacy of HDCT for this patient gro up.