Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors.
BACKGROUND
Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known.


METHODS
The authors performed a single-arm phase 2 study of the aromatase inhibitor letrozole at a dose of 2.5 mg daily in patients with unresectable ULMS with ER and/or PR expression confirmed by immunohistochemistry. Tumor assessments were performed at baseline, 6 weeks, 12 weeks, and every 8 weeks thereafter. Toxicity was monitored throughout treatment. The primary endpoint was the progression-free survival at 12 weeks.


RESULTS
A total of 27 patients was accrued, with a median of 2 prior treatment regimens (range, 0-9 treatment regimens). The median duration of protocol treatment was 2.2 months (range, 0.4 months-9.9 months). The 12-week progression-free survival rate was 50% (90% confidence interval, 30%-67%). The best response was stable disease in 14 patients (54%; 90% CI, 36%-71%). Three patients, all of whom had tumors expressing ER and PR in > 90% of tumor cells, continued to receive letrozole for > 24 weeks. The most common reason for treatment discontinuation was disease progression (85%). Letrozole was found to be well tolerated.


CONCLUSIONS
Letrozole met protocol-defined criteria as an agent with activity in patients with advanced ULMS. Patients with the longest progression-free survival rate were those whose tumors strongly and diffusely expressed ER and PR.
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Suzanne
S
George
Yang
Y
Feng
Judith
J
Manola
Marisa R
MR
Nucci
James E
JE
Butrynski
Jeffrey A
JA
Morgan
Nikhil
N
Ramaiya
Richard
R
Quek
Richard T
RT
Penson
Andrew J
AJ
Wagner
David
D
Harmon
George D
GD
Demetri
Carolyn
C
Krasner
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000378:metabolism; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000077289:Letrozole
aromatase inhibitor; leiomyosarcoma; letrozole; phase 2 clinical trial