Effective oral combination metronomic chemotherapy with low toxicity for the management of castration-resistant prostate cancer.

Prostate cancer (PC) was previously believed to be a chemoresistant disease. In recent years taxane-based chemotherapy has been shown to prolong survival in patients with castration-resistant prostate cancer (CRPC). It remains to be shown, however, which type of chemotherapy provides the most beneficial effect with the least amount of side effects. Seventeen patients with chemonaive CRPC were enrolled in a pilot study evaluating an orally administered chemo-hormonal treatment regimen using a weekly sequential combination called KEES; consisting of ketoconazole in combination with cyclophosphamide or etoposide in combination with estramustine administered on alternate weeks. Prednisone was administered throughout the treatment period. Prostate-specific antigen (PSA) response and acute and chronic toxicities were evaluated. Seventeen patients with CRPC were treated; eleven patients demonstrated a median reduction in PSA of 87% (range 26-99%). Ten (59%) patients responded with a decrease in PSA >50%. Thrombocytopenia and anaemia were the most common side effects. One study fatality was reported, however, it was unclear whether this was treatment related. In conclusion, KEES may be a promising option for patients with CRPC, resulting in a clear reduction in PSA with limited toxicity. Further clinical evaluation of this metronomic chemohormonal combination is underway.