HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM-CELL SUPPORT FOR THE TREATMENT OF METASTATIC BREAST-CANCER

The overall median survival of women with advanced or high risk primary disease has not changed with conventional chemotherapy. Regimens employing high dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early Phase I studies of patients with advanced refractory disease demonstrated the feasibility of administering agents in doses 5-30 times higher than those conventionally used. These studies achieved high response rates of short duration. Second generation studies combined an induction phase followed by one high dose intensification at the time of maximum tumor response. To date, between 15 and 30% of women with metastatic disease remain progression free after being treated with this approach, with median lengths of follow-up approaching 36 months in the larger series. With the advent of hematologic support, such as blood stem cells and colony stimulating factors, the morbidity, mortality, and costs associated with this treatment have been reduced substantially. These supports now allow for two or more cycles of high dose intensification to be employed, to exploit the potential of dose intensity to optimize response. Recent single-institution studies using ABMT for high risk Stages II and III breast cancer have reported preliminary findings suggesting a prolonged disease free survival. The cooperative groups now have begun prospective randomized studies in high risk women with Stages II and III disease with 10 or more positive axillary lymph nodes, and soon will study the efficacy of ABMT in women with inflammatory or locally unresectable breast cancer (Stage IIIB).