METHODS OF USE OF MACROCYCLIC LACTONS AS A MEANS FOR THE REVERSAL OF MULTIPLE MEDICAMENT RESISTANCE IN CANCER AND OTHER CELLS

摘要

This invention describes methods for increasing the toxicity of a cytostatic hydrophobic chemotherapeutic agent against resistant tumor cells in mammals which comprise administering a multidrug resistant reversing agent to the mammal in connection with the administration of the cytostatic hydrophobic chemotherapeutic agent in an amount effective to increase the toxicity of the chemotherapeutic agent, wherein the multidrug resistant reversing agent is a macrocyclic lactone compound. Examples of the macrocyclic lactone compounds useful in the present invention include, but are not limited to, the LL-F28249 alpha - lambda series of compounds, the 23-oxo or 23-imino derivative thereof, the avermectins, the 22,23-dihydro derivatives thereof and the milbemycins. Compositions comprising the macrocyclic lactone compounds and the chemotherapeutic agents are also described herein.