Letrozole (CGS 20267). A phase I study of a new potent oral aromatase inhibitor of breast cancer.
BACKGROUND
Letrozole (CGS 20267), a triazole derivative, is a new, once-daily, oral nonsteroidal inhibitor of aromatase activity.


METHODS
In this Phase I trial, 23 heavily pretreated postmenopausal patients with metastatic breast cancer received letrozole at doses ranging from 0.1 to 5.0 mg once daily.


RESULTS
No hematologic, biochemical, or significant clinical toxicity was encountered. Serial steroid measurements were determined in 19 of these patients. Letrozole at all doses tested produced a marked suppression of plasma estrone, estradiol, estrone sulfate, and urine estrone and estradiol. This was observed within 24 hours of the initial dose of letrozole and resulted in a greater than 90% suppression of plasma and urinary estrogen levels within 2 weeks. Letrozole appears to be highly selective in its action and does not compromise glucocorticoid or mineralocorticoid production or thyroid function. Of the 21 evaluable patients, there were 2 with partial responses and 7 with stable disease.


CONCLUSIONS
Letrozole is a well tolerated, potent, and specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer.
Lipton
A
A
Department of Medicine, M. S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Demers
L M
LM
Harvey
H A
HA
Kambic
K B
KB
Grossberg
H
H
Brady
C
C
Adlercruetz
H
H
Trunet
P F
PF
Santen
R J
RJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole