title: Intensive chemotherapy with autologous bone marrow transfusion as primary treatment in women with breast cancer and more than five involved axillary lymph nodes.
abstract: Patients with breast cancer and a high number of involved axillary lymph nodes have a poor prognosis, despite adjuvant chemotherapy. The 5-year 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 being sought for this group of patients. The aim of the present study was the evaluation of the efficacy of high-dose chemotherapy combined with autologous bone marrow support. 24 patients with a primary breast cancer with more than five involved axillary lymph nodes received, after surgery, six courses of induction chemotherapy followed by ablative chemotherapy and reinfusion of autologous bone marrow. All patients were premenopausal or less than 2 years postmenopausal. Induction chemotherapy consisted of methotrexate (MTX) 1.5 g/m2 intravenous (i.v.) and 5-fluorouracil (5-FU) 1.5 g/m2 i.v. on day 1, prednisone 40 mg/m2 orally on days 2-14, doxorubicin 50 mg/m2 i.v. and vincristine 1 mg/m2 i.v. on day 14. Courses were repeated six times every 4 weeks. 10 patients received cyclophosphamide 7 g/m2 i.v. and etoposide 1.5 g/m2 i.v. as intensive regimen, in 14 patients this comprised mitoxantrone 50 mg/m2 i.v. and thiotepa 800 mg/m2 i.v. Reinfusion of autologous marrow followed on day 7. Finally, patients received locoregional radiotherapy for extranodal disease and tamoxifen 40 mg daily orally 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 induction therapy, fever requiring i.v. antibiotics occurred in 4% of 144 courses, 14% of patients suffered from mucositis WHO grade 2-3, and the other patients had mucositis grade 1. During the ablative chemotherapy, 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-induced 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 and > 10 positive nodes, respectively, have relapsed after 18 and 36 months, both in the cyclophosphamide/etoposide regimen. Median observation 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.
authors.affiliation: Department of Internal Medicine, University Hospital Groningen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: de Graaf
authors.forename: P H
authors.initials: PH
authors.lastname: Willemse
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: P O
authors.initials: PO
authors.lastname: Mulder
authors.forename: W T
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: C T
authors.initials: CT
authors.lastname: Smit Sibinga
authors.forename: E
authors.initials: E
authors.lastname: van der Ploeg
authors.forename: W V
authors.initials: WV
authors.lastname: Dolsma
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D005472:Fluorouracil; D011241:Prednisone; D008727:Methotrexate