Summary
4′-Deoxydoxorubicin is a new anthracycline derivative. Experimentally, the drug shows efficacy against doxorubicin-resistant malignancies and, as compared to the parent compound, it has reduced potential for heart damage. This Phase I trial was conducted with a single dose intermittent schedule. 4′-Deoxydoxorubicin was given by rapid i.v. administration at doses of 20, 30, 35 and 40 mg/m2. A total of 25 adult patients with a variety of solid tumors received a median of two courses (1–4). Leukopenia was dose-related and dose-limiting. Occasionally severe thrombocytopenia was also encountered. Nonhematological toxic effects were mostly mild to moderate and were qualitatively similar to those commonly reported with doxorubicin. The frequency of local reactions was apparently increased but the incidence of alopecia and gastrointestinal distress was noticeably lower. There were no acute or chronic drug-induced cardiac effects. Antitumor activity was suggested in a patient with a carcinoma of the cardia. For Phase II trials, doses of 35 and 30 mg/m2 every 3–4 weeks may be recommended in good-risk and poor-risk patients, respectively.
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Arcamone F, Penco S, Redaelli S, Hanessian S: Synthesis and antitumor activity of 4′-deoxydaunorubicin and 4′-deoxyadriamycin. J Med Chem 19:1424–1425, 1976
Casazza AM, Savi G, Pratesi G, Di Marco A: Antitumor activity in mice of 4′-deoxydoxorubicin in comparison with doxorubicin. Eur J Cancer Clin Oncol 19:411–418, 1983
Giuliani FC, Kaplan NO: New doxorubicin analogs active against doxorubicin-resistant colon tumor xenografts in the nude mouse. Cancer Res 40:4682–4687, 1980
Giuliani FC, Coirin AK, Rice MR, Kaplan NO: Effect of 4′-doxorubicin analogs on heterotransplantation of human tumors in congenitally athymic mice. Cancer Treat Rep 65:1063–1075, 1981
Salmon SE, Liu RM, Casazza AM: Evaluation of new anthracycline analogs with the human tumor stem cell assay. Cancer Chemother Pharmacol 6:103–110, 1981
Di Marco A, Casazza AM, Dasdia T, Necco A, Pratesi G, Rivolta P, Velcich A, Zaccara A, Zunino F: Changes of activity of daunorubicin, adriamycin and stereoisomers following the introduction or removal of hydroxyl groups in the amino sugar moiety. Chem Biol Interact 19:291–302, 1977
Casazza AM, Di Marco A, Bonadonna G, Bonfante V, Bertazzoli C, Bellini O, Pratesi G, Sala L, Ballerini L: Effects of modifications in position 4 of the chromophore or in position 4′ of the amino-sugar, on the antitumor activity and toxicity of daunorubicin and doxorubicin. In ST Crooke and SD Reich (eds): Anthracycline: Current Status and New Developments. Academic Press, New York, 1980, pp 403–430
Casazza AM: Experimental evaluation of anthracycline analogs. Cancer Treat Rep 63:835–844, 1979
IMI 58, 4′-deoxydoxorubicin. Clinical Brochure, M. Cagnasso (ed), Farmitalia Carlo Erba, Milan, 1981
Formelli F, Pollini C, Casazza AM, di Marco A, Mariani A: Fluorescence assays and pharmacokinetic studies of 4′-deoxydoxorubicin and doxorubicin in organs of mice bearing solid tumors. Cancer Chemother Pharmacol 5:139–144, 1981
Rozencweig M, Dodion P, Nicaise C, Piccart M, Kenis Y: Approach to Phase I trials in cancer patients. In H. Cortes Funes and M Rozencweig (eds): New Approaches in Cancer Therapy. Raven Press, New York, 1982, pp 1–13
Sessa C, Kaplan S, Kaplan E, Varini M, Cavalli F: Phase I trial of i.v. weekly 4′-deoxydoxorubicin. Proc Am Soc Clin Oncol 2:24, 1983
Rozencweig M, Von Hoff DD, Staquet MJ, Schein PS, Penta JS, Goldin A, Muggia FM, Freireich EJ, De Vita VT Jr: Animal toxicology for early clinical trials with anticancer agents. Cancer Clin Trials 4:21–28, 1981
WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization, Geneva, 1979
Stanton GF, Wittes RE, Raymond V, Budman D, Shulman P, Kelsen D, Young CW: 4′-Deoxydoxorubicin (DXDX): a Phase I trial in patients (pts) with advanced cancer. Proc Am Assoc Cancer Res 24:153, 1983
Ferrari L, Rossi A, Brambilla C, Villani F, Bonfante V, Bonadonna G: Phase I study with 4′-deoxydoxorubicin (deoxyDX). Proc Am Assoc Cancer Res 24:163, 1983
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Rozencweig, M., Crespeigne, N. & Kenis, Y. Phase I trial with 4′-deoxydoxorubicin (esorubicin). Invest New Drugs 1, 309–313 (1983). https://doi.org/10.1007/BF00177414
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DOI: https://doi.org/10.1007/BF00177414