title: Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer--a quality assessment study.
abstract: From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support was used as an adjuvant treatment strategy for management of primary high-risk breast cancer patients with more than five positive nodes. This single institution study included 52 women aged < or = 56 years with primary operable breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment regimen consisted of at least three initial courses of FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral blood stem-cell reinfusion. This study focuses on quality control including evaluation of toxicity, supportive therapy and assessment of the stem-cell products. Cytokeratin 19 positive cells were found in the stem-cell product from 3/37 patients. Data regarding organ toxicity were used for evaluation of short- and long-term side effects. Substantial acute toxicity and frequent catheter-related infections were found. Long-term toxicities included reduced lung diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10), neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were grade 1-2 and reversible within two years. No treatment-related death occurred. Within a median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed. Recurrence-free survival was 75% and overall survival was 88% three years after the start of treatment. Overall, high-dose chemotherapy was relatively well tolerated, with manageable toxicity and an acceptable requirement of supportive therapy. Until now, high-dose chemotherapy has not proven superior to conventional-dose adjuvant chemotherapy, therefore it is necessary in the future to focus on well-designed randomized studies.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. inge.m.svane@dadlnet.dk
authors.forename: Inge M
authors.initials: IM
authors.lastname: Svane
authors.forename: Keld M
authors.initials: KM
authors.lastname: Homburg
authors.forename: Claus
authors.initials: C
authors.lastname: Kamby
authors.forename: Dorte L
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Ole
authors.initials: O
authors.lastname: Roer
authors.forename: Dorte
authors.initials: D
authors.lastname: Sliffsgaard
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johnsen
authors.forename: Steen W
authors.initials: SW
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D011785:Quality Assurance, Health Care; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D005472:Fluorouracil