Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A.
Thirty-one postmenopausal women with advanced breast cancer have been treated with the nonsteroidal competitive aromatase inhibitor CGS 16949A at p.o. doses of 0.3, 1, and 2 mg twice a day. All patients were assessed for response. Five patients, all treated with 1 mg twice daily, had objective evidence of response (two complete responses and three partial responses); disease stabilized in 17 patients. Minor side effects were reported by ten patients. Two further patients treated with 2 mg twice a day experienced persistent nausea which improved after dose reduction, and one patient, treated with 0.3 mg twice daily, developed a vasculitic rash requiring discontinuation of CGS 16949A. Estradiol levels measured in 24 patients were significantly suppressed 2 wk after starting CGS 16949A treatment at all doses used. Treatment with 2 mg twice a day lowered estradiol levels to a mean of 29% of pretreatment values which was significantly lower than the corresponding figure of 57% for patients treated with 0.3 mg twice daily. Aldosterone levels were significantly lowered below pretreatment values by the 1- and 2-mg twice daily doses. No clinically apparent cases of adrenocortical insufficiency occurred, although small changes in serum electrolyte levels were noted. The results indicate that CGS 16949A is an effective aromatase inhibitor, requiring further evaluation in the treatment of advanced breast cancer. The optimal dose is likely to be 1 mg twice a day.
Stein
R C
RC
Clinical Oncology Unit, St George's Hospital Medical School, London, England.
Dowsett
M
M
Davenport
J
J
Hedley
A
A
Ford
H T
HT
Gazet
J C
JC
Coombes
R C
RC
D000450:Aldosterone / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000032:analysis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004341:Drug Evaluation; D004573:Electrolytes / Q000097:blood; D004958:Estradiol / Q000097:blood; D017316:Fadrozole; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008593:Menopause; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000032:analysis
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004573:Electrolytes; D007093:Imidazoles; D009570:Nitriles; D011960:Receptors, Estrogen; D000450:Aldosterone; D004958:Estradiol; D017316:Fadrozole