Compositions, formulations, packaged pharmaceuticals, and methods of treatment by the sensitization of resistant tumors are provided. The compositions comprise a combination of a hedgehog pathway modulator, such as itraconazole or posaconazole, and a chemotherapeutic agent. Formulations disclosed include high-dose oral and injectable formulations of the hedgehog pathway modulator. Tumor cells in mammalian subjects treated with the hedgehog pathway modulator are sensitized to the effects of the chemotherapeutic agent, thus increasing the therapeutic index of the agent and reducing toxicity to the subject.
