A phase II study of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer.

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 Two patients however, were withdrawn from the study because of toxicity; one with a skin rash and one with severe vomiting.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.