Phase II study of oral 4-demethoxydaunorubicin in previously treated (except anthracyclines) metastatic breast cancer patients.

Forty-eight patients with metastatic breast cancer previously treated with cytostatics (except anthracyclines) underwent peroral treatment with 4-demethoxydaunorubicin (4-DMDR), a new daunorubicin analogue. Forty-three patients received greater than or equal to 2 cycles and have been evaluated. The mean age was 54 years, with 10 premenopausal and 33 postmenopausal patients. All the patients showed progressive disease. Performance status 0-2 (ECOG score) was recorded in 34, and 3 in 7 patients. Soft tissue metastases were recorded in 23, visceral in 10 and bone in 10 patients. 4-DMDR was administered in the dose of 15 mg/m2 perorally daily, on day 1, 2 and 3 (45 mg/m2 per cycle). Since there was no severe toxicity, after 2 cycles the dosage was increased to 60 mg/m2 per cycle. The patients received 2-6 cycles (median 3) and the total cumulative dose ranged from 90 to 300 mg/m2 (median 140 mg/m2). Objective response was observed in 10 patients (1 complete remission, 9 partial remissions) with a response rate of 23% (10/43). Soft tissue metastases were most responsive (8/23-35%). Two responses were observed in visceral organs. Response lasted 2-6+ months (median 4 months). Toxic side effects have been mild with myelotoxicity (grade I-II) observed in 23% of patients. Alopecia (grade 1-15 patients, grade II and III = 4 patients) was moderate. Nausea and vomiting (grade I-II) was present in 60% of patients. In all the patients MUGA scans (left ventricular ejection fraction) were in normal range, however, reversible ECG changes have been recorded in 4 patients (grade I = 3, grade II = 1). All the changes appeared on the 3rd day of the cycle but became normal before starting a new cycle. In conclusion, it should be emphasized that 4-DMDR administered perorally (45 mg/m2 per cycle) in previously treated (except anthracycline) metastatic breast cancer patients showed antitumor efficacy with a low incidence of toxic side effects. Further clinical studies, possibly with the dose escalation in the schedule we have used, will be needed in previously untreated breast cancer patients to determine exact antitumor activity of this new daunorubicin analogue.