High-intensity chemotherapy with peripheral blood progenitor cell support

In a series of clinical studies at Memorial Sloan-Kettering Cancer Center, we have used hematopoietic growth factors and peripheral blood-derived hematopoietic progenitor cells to facilitate delivery of multiple courses of high-dose chemotherapy at abbreviated treatment intervals. In these studies, we have demonstrated the feasibility of cross-over regimens involving induction chemotherapy with high-dose cyclophosphamide, supported by granulocyte colony-stimulating factor and followed by multiple peripheral blood leukapheresis to harvest progenitor cells. These cells are then used as rescue for the consolidation component of treatment, which, in the earlier-generation studies, consisted of a single course of high-dose carboplatin/etoposide/cyclophosphamide chemotherapy. In subsequent studies, patients received either four courses of high-dose carboplatin or carboplatin/cyclophosphamide or tandem courses of thiotepa. In all cases, the planned interval between treatments was 14 days, and the achieved median was approximately 16 days. These studies show that the administration of high-intensity regimens that deliver multiple courses of very high-dose chemotherapy at relatively brief intervals is feasible. Our current research focuses on exploiting these findings to devise disease-specific regimens for breast and ovarian cancer.