ABSTRACT
BACKGROUND: High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. METHODS: We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. RESULTS AND CONCLUSIONS: Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.
ABSTRACT
High-dose chemotherapy followed by autologous stem cell rescue has been associated with an increased overall response rate and improved progression-free survival for patients with metastatic breast cancer when compared retrospectively to standard therapy. The optimal source of stem cells - peripheral blood or autologous bone marrow - has not been determined. We present results from two high-dose regimens - ifosfamide, carboplatin, and etoposide (ICE) or mitoxantrone and thiotepa (MITT) followed by autologous stem cell rescue - and analyze the outcomes for patients based on the regimen used and the source of stem cells. Disease responsiveness at the time of high-dose therapy is the most important factor for determining outcome. The source of stem cells did not affect progression-free survival for either group.
ABSTRACT
Classical bone marrow transplantation collects bone marrow from a normal individual. This is infused into a patient rendered aplastic by high-dose chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and mortality from graft-vs-host and graft rejection phenomena. Autologous marrow transplantation, in which the marrow of the patient to be transplanted is harvested, cryopreserved, and stored until needed, is not so constrained. Although marrow cannot be collected from some individuals due to hypocellularity, fibrosis, or infiltration with malignant disease, the presence of peripheral blood stem cells in the circulation allows these individuals to be treated with autologous transplantation therapy. It has been postulated that these hematopoietic progenitors have advantages over bone marrow collected stem cells, including safer and less expensive collections and accelerated rates of hematopoietic recovery following high-dose therapy and stem cell reinfusion.
