Comparison of three approaches to doxorubicin therapy: Free doxorubicin, liposomal doxorubicin, and beta-glucuronidase-activated prodrug (HMR 1826)

Background: Three approaches to doxorubicin therapy are directly compared: free doxorubicin, liposomal doxorubicin and beta-glucuronidase-activated pr odrug (HMR 1826). Materials and Methods: The optimal dose of HMR 1826 was d etermined to be 200 mg/kg once a week and subsequent studies were carried o ut comparing HMR 1826 at 200 mg/kg 1x/wk, liposomal doxorubicin (Doxil) at 9 mg/kg 1x/wk and free doxorubicin at 7 mg/kg 1x/wk in seven different huma n tumor xenograft models. Results: All three forms of doxorubicin inhibited tumor growth with similar efficacy in each of the tumor models with the ex ception of MDA-MB-231 tumor xenografts, which were resistant to free doxoru bicin but sensitive to Doxil and HMR 1826. Overall less weight loss was obs erved with HMR 1826 treatment. Conclusions: The efficacy of HMR 1826 is equ al to or better than that of doxorubicin and Doxil at a safe dose and sched ule, indicating that the beta-glucuronidase activated prodrug approach is s afe and effective.