The administration of cytotoxic agents followed by the administration of
heat shock protein 90 inhibitors, such as ansamycins, has a synergistic
effect on the growth inhibition of cells. This synergy occurs at doses of
each cytotoxic agent that normally only causes minimal growth inhibition
of cells. Such combination therapy thus allows one to use lower doses of
cytotoxic agents to avoid or reduce their respective toxicity to patients
without compromising their growth inhibitory effects. Thus, these
combinations can be used for the treatment of an animal, preferably a
mammal, that has a cell proliferative disorder, whether the cells have
wild-type Rb or are Rb deficient or Rb negative. One such method,
directed to treating cell proliferative disorders includes the step of
administering a therapeutic effective amount of a cytotoxic agent
followed by administering a therapeutic effective amount of a heat shock
protein 90 inhibitor. The cytotoxic agent may be a microtubule-affecting
agent, topoisomerase II inhibitor, a platinum complex, paclitaxel, or a
paclitaxel derivative. The HSP90 inhibitor may be an ansamycin, radicicol
or a synthetic compound that binds to the ATP-binding site of HSP90.