Smart bombs versus blunderbusses: high-dose chemotherapy for breast cancer

Abstract

Perhaps no treatment in medical history had as meteoric a rise, or as humiliating a fall from grace, as high-dose chemotherapy for breast cancer. The concept was simple. Conventional-dose chemotherapy produced modest benefits for patients with metastatic or high-risk early-stage disease. 1 Weiss RB Woolf SH Demakos E Natural history of more than 20 years of node-positive primary breast carcinoma treated with cyclophosphamide, methotrexate, and fluorouracil-based adjuvant chemotherapy: a study by the Cancer and Leukemia Group B. J Clin Oncol. 2003; 21: 1825-1835 Crossref PubMed Scopus (55) Google Scholar So perhaps very high doses would produce better results. Supportive laboratory data showed a meaningful dose-response relation for chemotherapeutic drugs, and advances in haemopoietic support technology—eg, marrow autografting—helped such dose-escalation. The results of early non-randomised trials were encouraging. Complete remissions (some durable) were often reported, prompting speculation that high-dose chemotherapy might cure a few patients with metastases. In addition, up to 70% of patients who underwent such treatment after the discovery of heavy axillary involvement at primary surgery (a group with a very poor prognosis) achieved prolonged remission. However, the treatment was toxic (treatment-related death rates were as high as 10–20% in early studies), and by the standards of the time, expensive. The replacement of marrow by support with peripheral blood progenitors resulted in reduced mortality, shortened stays in hospital, and reduced costs.