New anthracycline analogs in advanced breast cancer.
To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.
Bonfante
V
V
Ferrari
L
L
Brambilla
C
C
Rossi
A
A
Villani
F
F
Crippa
F
F
Valagussa
P
P
Bonadonna
G
G
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003630:Daunorubicin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004341:Drug Evaluation; D015251:Epirubicin; D005260:Female; D006801:Humans; D015255:Idarubicin; D008875:Middle Aged; D009279:Naphthacenes / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D015251:Epirubicin; D004317:Doxorubicin; C030851:esorubicin; D015255:Idarubicin; D003630:Daunorubicin