ketoconazole + mitoxantrone + sargramostim

A multi-drug regimen combining the small-molecule antifungal and CYP3A inhibitor ketoconazole, the anthracenedione chemotherapeutic mitoxantrone, and the recombinant human GM-CSF cytokine sargramostim. In oncology, ketoconazole has been used to suppress adrenal and intratumoral androgen synthesis and to inhibit CYP-mediated drug metabolism, potentially enhancing chemotherapeutic exposure; mitoxantrone intercalates DNA and inhibits topoisomerase II, causing cytotoxicity; sargramostim stimulates myelopoiesis via GM-CSF receptor activation to reduce chemotherapy-induced neutropenia and may have immunomodulatory effects. A Phase II study evaluated mitoxantrone plus continuous oral ketoconazole in hormone-refractory (castration-resistant) prostate cancer, showing tolerability and antitumor activity; a clinical trial was designed to assess the triplet of ketoconazole, mitoxantrone, and GM-CSF (sargramostim) in progressive prostate cancer.[4][7][10][9][6]