Acute and Late Toxicity Following Adjuvant High-Dose Chemotherapy for High-Risk Primary Operable Breast Cancer A Quality Assessment Study

• Published in: Acta oncologica 2002, Vol.41 (7), p.675-683
• Main Authors: Svane, Inge M., Homburg, Keld M., Kamby, Claus, Nielsen, Dorte L., Roer, Ole, Sliffsgaard, Dorte, Johnsen, Hans E., Hansen, Steen W.
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carboplatin - administration & dosage; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Cyclophosphamide - administration & dosage; Drug Administration Schedule; Epirubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Gynecology. Andrology. Obstetrics; Hematopoietic Stem Cell Transplantation; Humans; Lymph Nodes - pathology; Mammary gland diseases; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Quality Assurance, Health Care; Survival Rate; Thiotepa - administration & dosage; Transplantation, Autologous; Tumors
• ISSN: 0284-186X; 1651-226X
• DOI: 10.1080/028418602321028300

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 &#104 56 years with primary operable breast cancer and &#83 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.