Preclinical Studies on the Potential Use of Swainsonine with High-DoseChemotherapy in Humans: Chemoprotective and Hemarestorative Properties

摘要

The overall goal of these pre-clinical studies is to optimize the therapeuticpotential of the novel agent, swainsonine, for utilization in the management of myelosuppression associated with high-dose chemotherapy, a method of treatment currently being used for human metastatic and high-risk primary breast cancer. Our initial studies have focused on determining the optimal dose, schedule and timing of swainsonine treatment to protect against the toxicity associated with multiple cycles of chemotherapy, administered similar to that used in humans. Our studies have clearly demonstrated, for the first time, that survival in mice receiving methotrexate and swainsonine is 7-fold greater than that in mice receiving methotrexate only. Thus swainsonine is able to significantly protect mice from the chemotoxicity associated with up to 3 cycles of methotrexate. The relationship between this increase in survival and swainsonine's known effect on hematopoietic cells is currently under study in non-tumor bearing and tumor-bearing mice.