TANDEM HIGH-DOSE CHEMOTHERAPY SUPPORTED BY HEMATOPOIETIC PROGENITOR CELLS YIELDS PROLONGED SURVIVAL IN STAGE-IV BREAST-CANCER

The aim of this phase II study was to determine the feasibility of usi ng two (tandem) courses of high-dose alkylating agents with bone marro w or peripheral blood progenitor cell support in women with stage IV b reast cancer, Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II tri al of high-dose cyclophosphamide 7500 mg/m(2) and thiotepa 675 mg/m(2) (CST) followed within 180 days by high-dose melphalan (M) 140 mg/m(2) . Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic p rogenitor cells were used to support high-dose C+T and high-dose M. Tw enty-seven women were enrolled in this trial, The median age was 45 ye ars (range 32-56), The median PS was 0 and all patients had achieved e ither a CR (4/27, 15%) or PR (23/27, 85%) to coventional chemotherapy, All 27 women underwent high dose C+T, The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infe ctious complications, Following C+T, the median time to hematologic re covery for neutrophils (ANC >500 cells/mu 1) was 12 days and for plate lets (>20 000 cell/mu l), 23 days, Following C+T, 18 of 22 patients re ceived high dose M; the predominant toxicities were nausea, vomiting ( 70%), and mucositis (91%), The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days, The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%), With median follow-up of 24 months, the actuarial freedom from relapse or treatmen t failure is 56% at 24 months, At 30 months 56% of patients are alive, For patients who achieve a CR or PR the actuarial freedom from relap se or treatment failure at 24 months is 88%, In women with stage IV br east cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free s urvival.