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

Abstract

BACKGROUND:

Three approaches to doxorubicin therapy are directly compared: free doxorubicin, liposomal doxorubicin and beta-glucuronidase-activated prodrug (HMR 1826).

MATERIALS AND METHODS:

The optimal dose of HMR 1826 was determined to be 200 mg/kg once a week and subsequent studies were carried out 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 human tumor xenograft models.

RESULTS:

All three forms of doxorubicin inhibited tumor growth with similar efficacy in each of the tumor models with the exception of MDA-MB-231 tumor xenografts, which were resistant to free doxorubicin but sensitive to Doxil and HMR 1826. Overall less weight loss was observed with HMR 1826 treatment.

CONCLUSIONS:

The efficacy of HMR 1826 is equal to or better than that of doxorubicin and Doxil at a safe dose and schedule, indicating that the beta-glucuronidase activated prodrug approach is safe and effective.

• Authors: R Woessner, Z An, X Li, R M Hoffman, R Dix, A Bitonti
• Journal: Anticancer research (Anticancer Res) 2000 Jul-Aug Vol. 20 Issue 4 Pg. 2289-96 ISSN: 0250-7005 [Print] Greece
• PMID: 10953287 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Glucuronates
• Liposomes
• N-(4-glucuronyl-3-nitrobenzyloxycarbonyl)doxorubicin
• Prodrugs
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (therapeutic use)
• Doxorubicin (administration & dosage, analogs & derivatives, therapeutic use)
• Drug Administration Schedule
• Drug Carriers
• Female
• Glucuronates (therapeutic use)
• Humans
• Liposomes (administration & dosage)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy)
• Prodrugs (therapeutic use)