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Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors
Author(s) -
George Suzanne,
Feng Yang,
Manola Judith,
Nucci Marisa R.,
Butrynski James E.,
Morgan Jeffrey A.,
Ramaiya Nikhil,
Quek Richard,
Penson Richard T.,
Wagner Andrew J.,
Harmon David,
Demetri George D.,
Krasner Carolyn
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28476
Subject(s) - letrozole , medicine , aromatase inhibitor , discontinuation , aromatase , estrogen receptor , clinical endpoint , progressive disease , estrogen , exemestane , oncology , progression free survival , fulvestrant , breast cancer , gastroenterology , gynecology , urology , cancer , chemotherapy , clinical trial
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. Cancer 2014;120:738–743 . © 2013 American Cancer Society .