treatment for metastatic breast cancer. The rationale for this 
approach comes from the observation that many chemotherapy drugs, 
particularly alkylating agents, have steep tumoricide dose-response 
curves. In some instances the response curves are so steep that 
doubling drug doses may increase cell kill by as much as 10-fold (1). 
With the use of autologous bone marrow rescue, it has been possible 
to increase drug doses by 4 to 10-fold over standard doses. Several 
observations suggest that this strategy may provide a therapeutic 
benefit over conventional chemotherapy. First, an analysis of the 
relationship between dose-intensity of adjuvant chemotherapy in 
breast cancer and disease free survival, performed by Hryniuk and 
Levine, suggests that DFS can be improved through the use of more 
dose-intensive regimens (2). Similar analyses carried out by 
DeVita, et al. and Kwak, et al. for the treatment of diffuse 
aggressive lymphomas reached similar conclusions (3,4). Second, 
studies of high-dose chemotherapy with ABMT in metastatic breast 
cancer, testicular carcinoma, Hodgkin's and non-Hodgkin's 
lymphomas and leukemias demonstrate that the CR and PR rate is 
significantly increased over that achieved with conventional dose 
chemotherapy (5-8). 
Studies of high dose chemotherapy and ABMT following 3-4 cycles of 
induction therapy in chemotherapy responsive breast cancer have 
shown very high complete response rates of 50%. While the median 
time to treatment failure and median survival appears to be no 
better than that achieved with conventional chemotherapy, three 
trials have reported that 15 - 20% of all patients undergoing ABMT 
are alive and disease-free at 3 years (9-11). This compares 
favorably with the results of conventional chemotherapy where 
fewer than 10% of patients are generally disease-free at 3 years 
(12,13). Prospective randomized studies are currently underway to 
determine whether high dose chemotherapy and ABMT offer any 
definitive advantages over dose-intensive chemotherapy alone. 
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Recombinant DNA Research, Volume 16 
