Summary
Idarubicin (4-demethoxydaunorubicin: DMDNR) is an orally active analogue of daunorubicin that has shown promising activity in animal and early clinical studies. We gave idarubicin in a phase II study to patients with advanced breast cancer unresponsive to hormonal manipulation and in some cases to standard chemotherapeutic agents. Idarubicin was given orally every 21 days at a starting dose of 40 mg/m2 with dose escalation until myelosuppression occurred. Nadir blood counts showed that patient compliance was good. Of 33 patients studied, 32 are evaluable for response: 4 (13%) had partial responses (95% confidence interval 1%–23%) with a duration of response between 32 and 59 weeks; 8 (25%) had static disease for between 17 and 48 weeks; and 20 failed to respond. For patients not previously exposed to chemotherapy, the response rate was 3/19 (16%). Toxicity was mild, with little or no gastro-intestinal disturbance in the majority of patients, no severe haematological toxicity and little alopecia. Two patients however, were withdrawn from the study because of toxicity; one with a skin rash and one with severe vomiting. Idarubicin produces little toxicity when given orally at a dose of 40 mg/m2 every 21 days, but its activity in breast cancer is insufficient to justify its further use with this schedule. Further studies should be undertaken only if direct comparison can be made with doxorubicin.
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Arcamone F, Bernardi L, Giardino P, Patelli B, DiMarco A, Casazza AM, Pratesi G, Reggiani P (1976) Synthesis and antitumour activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin and their β anomers. Cancer Treat Rep 60:829–834
Bastholt L, Dalmark M (1987) Phase II study of Idarubicin given orally in the treatment of anthracycline-naive advanced breast cancer patients. Cancer Treat Rep 71 (5): 451–454
Berman E, Wittes RE, Leyland-Jones B, Casper ES, Gralla RJ, Koward J, Williams L, Boratz R, Young CW (1983) Phase I and clinical pharmacology studies of intravenous and oral administration of 4-demethoxydaunorubicin in patients with advanced cancer. Cancer Res 43: 6069–6101
Bonfante V, Ferrari L, Brambilla C, Rossi A, Villani F, Crippa F, Valagussa P, Bonadenna G (1986) New anthracycline analogs in advanced breast cancer. Eur J Cancer Clin Oncol 22: 1379–1385
Casazza AM, Bertazzoli C, Pratesi G (1979) Anti-leukaemic activity and cardiac toxicity of 4-demethoxydaunorubicin (4-DMDNR). Proc Am Assoc Cancer Res 20: 16
Casazza AM, Pratesi G, Giuliani F, Di Marco A (1980) Antileukaemic activity of 4-demethoxydaunorubicin in mice. Tumori 66: 549–564
Di Marco A, Casazza AM, Pratesi G (1977) Antitumour activity of 4-demethoxydaunorubicin administered orally. Cancer Treat Rep 61: 893–894
Di Marco A, Zunio F, Casazza AM (1978) Comparison of biochemical and biological methods in the evaluation of new anthracycline drugs. Antibiot Chemother 25: 12–20
Farmitalia Carlo Erba (1981) 4-demethoxydaunorubicin investigational brochure
Kaplan S, Sessa C, Willems Y, Pacciorini MA, Tamasia V, Cavalli F (1984) Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses. Invest New Drugs 2: 281–286
Kavanagh JJ, Yeung KY, Savaraj N, Krakoff IH (1985) Phase I clinical evaluation of oral and intravenous 4-demethoxydaunorubicin. Eur J Cancer Clin Oncol 21: 1187–1189
Kolaric K, Mechi Z, Potrebica V, Sopkova B (1987) Phase II study of oral 4-demethoxydaunorubicin in previously treated (except anthracyclines) metastatic breast cancer patients. Oncology 44: 82–86
Lambertenghi-Deliliers G, Pogliani E, Maiolo AT, Pacciorini MA, Polli EE (1983) Therapeutic activity of 4-demethoxydaunorubicin (idarubicin) in adult acute leukaemia. Tumori 69: 515–519
Lionetto R, Pronzato P, Conte PF, Sertoli MR, Amoroso D, Rosso R (1986) Idarubicin in advanced breast cancer: A phase II study. Cancer Treat Rep 70: 1439–1440
Lopez M, Di Lauro L, Papaldo P, Lazzaro B, Ganzina F, Di Petro N (1986) Phase II trial with oral 4-demethoxydaunorubicin (DMDR) in advanced breast cancer. Invest New Drugs 4: 39–42
Martoni A, Pacciarini MA, Pannuti F (1985) Activity of 4-demethoxydaunorubicin by the oral route in advanced breast cancer. Eur J Cancer Clin Oncol 21: 803–806
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Caner 47: 207–214
Wander H-E, Meyer D, Schuff-Werner P, Nagel GA (1986) Phase-II trial of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. Onkologie 9: 236–238
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Stuart, N.S.A., Cullen, M.H., Priestman, T.J. et al. A phase II study of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. Cancer Chemother. Pharmacol. 21, 351–354 (1988). https://doi.org/10.1007/BF00264204
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DOI: https://doi.org/10.1007/BF00264204