New Developments in High-Dose Chemotherapy for Breast Cancer

Abstract

A hint is given that escalation in chemotherapy dose might improve outcome for women with breast cancer by the results of single-arm studies of highdose chemotherapy (HDC) with autologous stem cell rescue (Gradishar et al. 1996). Response rates, and in some instances survival rates, also appear to be superior following a single cycle of myeloablative chemotherapy with bone marrow (BM) or peripheral blood progenitor cells (PBPC) support when compared to lower-dose regimens. In addition, long-term survival (up to 8 years) has been observed in patients who would otherwise have been expected to live a relatively short time (Peters 1995). In response to these promising reports, the use of HDC for the treatment of breast cancer has grown and changed dramatically over the last decade. In the USA, the percentage of autotransplants for breast cancer has increased from 16% to 40% of all autotransplants, so that now breast cancer is the most common indication for this therapy (Antman et al. 1997). The proportion of breast cancer autotransplants for local disease has increased from 7% to about 50% (Antman et al. 1997). The impact this has had on the treatment of breast cancer worldwide is reflected in the number of publications cited in a Medline search of “highdose chemotherapy” and “breast cancer,” which yielded over 700 entries since the first report of HDC for breast cancer in 1982. Although the early mortality from breast cancer HDC procedures was as high as 22%, it is now less than 5% (Antman et al. 1997). Improved control of acute toxicities and supportive care has greatly simplified this treatment. More rapid engraftment with the use of PBPC and the use of hematopoietic growth factors (HGF) and oral prophylactic antibiotics have allowed an increase in the proportion of care given in the outpatient setting (Ayash et al. 1994, Gianni et al. 1997 a), and reduced the costs substantially (Gilbert 1996). These factors in part explain the widespread adoption of HDC as a treatment for breast cancer. More than 95% of autotransplants for breast cancer in the USA have been performed outside of clinical trials (Antman et al. 1997), possibly due to due to a belief that, as stated by one US physician, “the issue is whether patients are randomly assigned to treatment we believe has no hope of cure, or to a treatment that does have a chance of cure” (Rushing 1997). A survey of oncologists conducted at the 1995 meeting of the American Society of Clinical Oncology gives additional insight into the dilemma. Besides the belief that randomized trials were no longer necessary because the phase II data had already provided sufficient data, problems cited for not putting patients on trial included the effort and time necessary and patient preferences (either wanting HDC or fearing it because of the toxicity) (Mathew 1995).