INTENSIVE CHEMOTHERAPY WITH AUTOLOGOUS BONE-MARROW TRANSFUSION AS PRIMARY-TREATMENT IN WOMEN WITH BREAST-CANCER AND MORE THAN 5 INVOLVED AXILLARY LYMPH-NODES

Patients with breast cancer and a high number of involved axillary lym ph nodes have a poor prognosis, despite adjuvant chemotherapy. The 5-y ear disease-free survival(DFS) in this group amounts to 30-40% and the 10-year DFS is only 15-20%. Therefore, new treatment modalities are b eing sought for this group of patients. The aim of the present study w as the evaluation of the efficacy of high-dose chemotherapy combined w ith autologous bone marrow support. 24 patients with a primary breast cancer with more than five involved axillary lymph nodes received, aft er surgery, six courses of induction chemotherapy followed by ablative chemotherapy and reinfusion of autologous bone marrow. All patients w ere premenopausal or less than 2 years postmenopausal. Induction chemo therapy consisted of methotrexate (MTX) 1.5 g/m(2) intravenous (i.v.) and 5-fluorouracil (5-FU) 1.5 g/m(2) i.v. on day 1, prednisone 40 mg/m (2) orally on days 2-14, doxorubicin 50 mg/m(2) i.v. and vincristine 1 mg/m(2) i.v. on day 14. Courses were repeated six times every 4 weeks . 10 patients received cyclophosphamide 7 g/m(2) i.v. and etoposide 1. 5 g/m(2) i.v. as intensive regimen, in 14 patients this comprised mito xantrone 50 mg/m(2) i.v. and thiotepa 800 mg/m(2) i.v. Reinfusion of a utologous marrow followed on day 7. Finally, patients received locoreg ional radiotherapy for extranodal disease and tamoxifen 40 mg daily or ally over a period of 2 years. The median age of patients was 42 years , range 29-54. The median number of involved nodes was 10. During indu ction therapy, fever requiring i.v. antibiotics occurred in 4% of 144 courses, 14% of patients suffered from mucositis WHO grade 23, and the other patients had mucositis grade 1. During the ablative chemotherap y, 1 patient died, 6 developed septicaemia, 5 showed mucositis grade 3 -4 and the other patients had mucositis grade 1 or 2. In the follow-up , 1 patient died from acute cardiac failure. Reversible radiation-indu ced pneumonitis occurred in 7 out of 14 irradiated patients; symptoms started directly following radiotherapy and lasted for several weeks, but disappeared in due course. During follow-up, 2 patients with six a nd > 10 positive nodes, respectively, have relapsed after 18 and 36 mo nths, both in the cyclophosphamide/etoposide regimen. Median observati on is 3 years, disease-free survival at 5 years is predicted to be 84% . Intensive treatment in these patients with high numbers of involved axillary lymph nodes is a toxic regimen, but may improve the chance of surviving free of disease.