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 prodrug (HMR 1826).


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.
Woessner
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R
Aventis Pharmaceuticals, Bridgewater, NJ 08807, USA.
An
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Li
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Hoffman
R M
RM
Dix
R
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Bitonti
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004337:Drug Carriers; D005260:Female; D005965:Glucuronates / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011355:Prodrugs / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005965:Glucuronates; D008081:Liposomes; C114198:N-(4-glucuronyl-3-nitrobenzyloxycarbonyl)doxorubicin; D011355:Prodrugs; D004317:Doxorubicin