HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM-CELL SUPPORT FOLLOWED BY POSTTRANSPLANTATION DOXORUBICIN AS INITIAL THERAPY FOR METASTATIC BREAST-CANCER

High-dose chemotherapy is associated with a high complete response rat e and possibly some survival advantage in patients with metastatic bre ast cancer, We designed a clinical trial consisting of a two-step high -dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-on e patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (C y; 5000 mg/m(2)), followed by granulocyte colony-stimulating factor. P eripheral blood stem cells were collected, Subsequently, patients rece ived Cy (6000 mg/m(2)), thiotepa (500 mg/m(2)), and carboplatin (800 m g/m(2)) (CTCb) with hematopoietic rescue, Upon recovery of hematopoiet ic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m(2)) were delivered, After Cy, nine patients (45%) developed neut ropenic fevers. There were no episodes of bacteremia. Patients receive d CTCb 37 days after starting Cy and had a hospital stay of 19 days. A fter CTCb, the median number of days to an absolute neutrophil count > 5 x 10(9)/liter was 8, and the median number of days to a platelet cou nt >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients . There were no hemorrhagic complications. Fifty-five of the 63 planne d courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median tim e to the second Dox cycle was 28 days, and to the last cycle was 30 da ys. Three episodes of neutropenic fevers were observed. Two patients d eveloped herpes zoster. This regimen is feasible, with acceptable toxi city.