Preliminary Phase II Experience with 4′Epidoxorubicin

Ferrazzí, Eros; Nicoletto, Ornella; Vinante, O.; Maraglino, G.; Fornasiero, A.; Pagnin, P.; Dagnini, G; Fiorentino, M. V.

doi:10.1007/978-94-009-7630-6_51

Cited by 2 publications

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“…4'-Epidoxorubicin, in similarity to doxorubicin, has been demonstrated to interfere with nucleic acid synthesis (15). The toxicity, pharmacological properties, mechanism of action, and activity in a variety of tumor models have been reported (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(37)(38)(39)(40), and the analog has been undergoing clinical pharmacokinetic investigation and Phase I and II trial (31)(32)(33)(34)(35)(36).…”

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confidence: 99%

The effectiveness of the anthracycline analog 4′-epidoxorubicin in the treatment of experimental tumors: a review

1985

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The current report presents the data of the Division of Cancer Treatment of the National Cancer Institute (NCI) on the antitumor activity of the anthracycline antibiotic 4'-epidoxorubicin in experimental tumor systems. Direct comparisons are made with doxorubicin in individual experiments, and the data are related to those of earlier studies in the form of a review of experimental activity, in order to assess the relative activity of 4'-epidoxorubicin and doxorubicin. The experimental test models utilized by the NCI for these studies included the leukemias P388 and L1210, B-16 melanoma, Lewis lung carcinoma, the colon tumors 26 and 38, and the mammary tumors CD8F1 and C3H16/C. The human tumors growing in xenograft in athymic mice included the models LX-1 lung tumor, CX-1 colon tumor, and MX-1 mammary tumor. Additional comparisons were made with the tumor models Gross leukemia, sarcoma 180, MSV-induced sarcoma, MS-2 tumor, and a variety of human tumors growing in athymic mice, as well as with in vivo toxicologic and in vitro cytotoxicity models. Although for 4'-epidoxorubicin there is only a minimal alteration of the configuration of the doxorubicin molecule, quantitative comparison of 4'-epidoxorubicin and doxorubicin revealed not only similarities but also differences in biological activity. Both drugs showed activity against a broad spectrum of experimental tumors, with 4'-epidoxorubicin more effective against some tumors and equally effective against others. 4'-Epidoxorubicin evidenced less toxicity than doxorubicin in both acute and chronic toxicity studies with retention of therapeutic effectiveness and showed reduced cardiotoxicity. With 4'-epidoxorubicin there resulted a higher therapeutic index and therapeutic ratio, permitting the use of higher dosage and a greater margin of safety. The preclinical differences in therapeutic and toxicologic manifestations of 4'-epidoxorubicin, reflecting apparent alterations in pharmacologic properties and mode of action in comparison with doxorubicin, support the broad spectrum clinical trials of this already-demonstrated clinically active drug.

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