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Clinical Sarcoma Research
Published in: Clinical Sarcoma Research 1/2014

Open Access 01-12-2014 | Research

Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors

Authors: Eirini Thanopoulou, Khin Thway, Komel Khabra, Ian Judson

Published in: Clinical Sarcoma Research | Issue 1/2014

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Abstract

Background

Aromatase inhibitors (AIs) have not been used consistently as part of the management of hormone receptor positive uterine leiomyosarcomas (ULMS). As a result, the published data regarding the efficacy of AIs in this subtype of ULMS are sparse.

Methods

We performed a retrospective electronic medical record review of patients with ULMS treated with an AI, in the 1st or the 2nd line setting, at the Sarcoma Unit of the Royal Marsden Hospital between 2001 and 2012. We assessed progression-free survival (PFS), objective response and toxicities and explored the correlation of the intensity of the hormone receptor status, as well as of the grade with PFS.

Results

Sixteen patients with measurable advanced ULMS were treated with an AI in our unit. All of them were oestrogen receptor (ER) and progesterone receptor (PgR) positive. Letrozole was used in all patients as 1st line endocrine therapy, while exemestane was mainly prescribed as 2nd line (83%). Median PFS in 1st line was 14 months (95% CI: 0 – 30 months), and prolonged PFS was more likely to be observed in patients with low grade compared to high grade ULMS (20 months vs. 11 months), and in moderately/strongly ER positive compared to weakly ER positive ULMS (20 months vs. 12 months). Best response was partial response (PR) in 2/16 patients (12.5%) and clinical benefit (CB), defined as complete response (CR) + PR + stable disease ≥6 months, was observed in 10/16 patients (CB rate (CBR) 62.5%). Median duration of 2nd line was 3 months and median PFS was not reached. The 1-year progression-free rate for the 2nd line AI was 80%. Best response was PR in one patient and CBR was 50%. AIs were well tolerated in both lines of treatment.

Conclusions

In this population of patients with hormone positive ULMS, AIs achieved a significant CBR (62.5%) in 1st line, which was retained in 2nd line (CBR: 50%). The relatively prolonged median PFS (14 months), along with the favourable toxicity profile could place AIs among the first choices of systemic treatment in hormone positive ULMS, preferably in strongly positive (>90%), and/ or low grade and low volume disease.
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Literature
1.
Thanopoulou E, Judson I: Hormonal therapy in gynecological sarcomas. Expert Rev Anticancer Ther. 2012, 12: 885-894. 10.1586/era.12.74CrossRefPubMed
2.
D’Angelo E, Prat J: Uterine sarcomas: a review. Gynecol Oncol. 2010, 116: 131-139. 10.1016/j.ygyno.2009.09.023CrossRefPubMed
3.
Reed NS, Mangioni C, Malmstrom H, Scarfone G, Poveda A, Pecorelli S, Tateo S, Franchi M, Jobsen JJ, Coens C, Teodorovic I, Vergote I, Vermorken JB: Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer. 2008, 44: 808-818. 10.1016/j.ejca.2008.01.019CrossRefPubMed
4.
Omura GA, Blessing JA, Major F, Lifshitz S, Ehrlich CE, Mangan C, Beecham J, Park R, Silverberg S: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol. 1985, 3: 1240-1245.PubMed
5.
Hensley ML, Ishill N, Soslow R, Larkin J, Abu-Rustum N, Sabbatini P, Konner J, Tew W, Spriggs D, Aghajanian CA: Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: Results of a prospective study. Gynecol Oncol. 2009, 112: 563-567. 10.1016/j.ygyno.2008.11.027CrossRefPubMed
6.
Hensley ML, Blessing JA, Mannel R, Rose PG: Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008, 109: 329-334. 10.1016/j.ygyno.2008.03.010PubMedCentralCrossRefPubMed
7.
Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC, Creasman W, Yordan E: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985, 55: 1648-1653. 10.1002/1097-0142(19850415)55:8<1648::AID-CNCR2820550806>3.0.CO;2-7CrossRefPubMed
8.
Sanfilippo R, Grosso F, Jones RL, Banerjee S, Pilotti S, D’Incalci M, Dei Tos AP, Raspagliesi F, Judson I, Casali PG: Trabectedin in advanced uterine leiomyosarcomas: a retrospective case series analysis from two reference centers. Gynecol Oncol. 2011, 123: 553-556. 10.1016/j.ygyno.2011.08.016CrossRefPubMed
9.
van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schoffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012, 379: 1879-1886. 10.1016/S0140-6736(12)60651-5CrossRefPubMed
10.
Akhan SE, Yavuz E, Tecer A, Iyibozkurt CA, Topuz S, Tuzlali S, Bengisu E, Berkman S: The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study. Gynecol Oncol. 2005, 99: 36-42. 10.1016/j.ygyno.2005.05.019CrossRefPubMed
11.
Bodner K, Bodner-Adler B, Kimberger O, Czerwenka K, Leodolter S, Mayerhofer K: Estrogen and progesterone receptor expression in patients with uterine leiomyosarcoma and correlation with different clinicopathological parameters. Anticancer Res. 2003, 23: 729-732.PubMed
12.
Kitaoka Y, Kitawaki J, Koshiba H, Inoue S, Ishihara H, Teramoto M, Honjo H: Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas: correlation with clinical parameters. J Steroid Biochem Mol Biol. 2004, 88: 183-189. 10.1016/j.jsbmb.2003.11.013CrossRefPubMed
13.
Leitao MM, Hensley ML, Barakat RR, Aghajanian C, Gardner GJ, Jewell EL, O’Cearbhaill R, Soslow RA: Immunohistochemical expression of estrogen and progesterone receptors and outcomes in patients with newly diagnosed uterine leiomyosarcoma. Gynecol Oncol. 2012, 124: 558-562. 10.1016/j.ygyno.2011.11.009CrossRefPubMed
14.
Hardman MP, Roman JJ, Burnett AF, Santin AD: Metastatic uterine leiomyosarcoma regression using an aromatase inhibitor. Obstet Gynecol. 2007, 110: 518-520. 10.1097/01.AOG.0000267533.56546.c2CrossRefPubMed
15.
Ioffe YJ, Li AJ, Walsh CS, Karlan BY, Leuchter R, Forscher C, Cass I: Hormone receptor expression in uterine sarcomas: prognostic and therapeutic roles. Gynecol Oncol. 2009, 115: 466-471. 10.1016/j.ygyno.2009.08.014CrossRefPubMed
16.
O’Cearbhaill R, Zhou Q, Iasonos A, Soslow RA, Leitao MM, Aghajanian C, Hensley ML: Treatment of advanced uterine leiomyosarcoma with aromatase inhibitors. Gynecol Oncol. 2010, 116: 424-429. 10.1016/j.ygyno.2009.10.064CrossRefPubMed
17.
George S, Feng Y, Manola J, Nucci MR, Butrynski JE, Morgan JA, Ramaiya N, Quek R, Penson RT, Wagner AJ, Harmon D, Demetri GD, Krasner C: Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors. Cancer. 2014, 120: 738-743. 10.1002/cncr.28476CrossRefPubMed
18.
Coindre JM, Nguyen BB, Bonichon F, de Mascarel I, Trojani M: Histopathologic grading in spindle cell soft tissue sarcomas. Cancer. 1988, 11: 2305-9.CrossRef
19.
Bell SW, Kempson RL, Hendrickson MR: Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol. 1994, 18: 535-558. 10.1097/00000478-199406000-00001CrossRefPubMed
20.
Veras E, Zivanovic O, Jacks L, Chiappetta D, Hensley M, Soslow R: “Low-grade leiomyosarcoma” and late-recurring smooth muscle tumors of the uterus: a heterogenous collection of frequently misdiagnosed tumors associated with an overall favorable prognosis relative to conventional uterine leiomyosarcomas. Am J Surg Pathol. 2011, 35: 1626-1637. 10.1097/PAS.0b013e31822b44d2CrossRefPubMed
21.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer. 2009, 45: 228-247. 10.1016/j.ejca.2008.10.026CrossRefPubMed
22.
Pautier P, Genestie C, Rey A, Morice P, Roche B, Lhomme C, Haie-Meder C, Duvillard P: Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma. Cancer. 2000, 88: 1425-1431. 10.1002/(SICI)1097-0142(20000315)88:6<1425::AID-CNCR21>3.0.CO;2-3CrossRefPubMed
23.
D’Angelo E, Espinosa I, Ali R, Gilks CB, Rijn M, Lee CH, Prat J: Uterine leiomyosarcomas: tumor size, mitotic index, and biomarkers Ki67, and Bcl-2 identify two groups with different prognosis. Gynecol Oncol. 2011, 121: 328-333. 10.1016/j.ygyno.2011.01.022CrossRefPubMed
24.
Giuntoli RL, Garrett-Mayer E, Bristow RE, Gostout BS: Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma. Gynecol Oncol. 2007, 106: 82-88. 10.1016/j.ygyno.2007.02.031CrossRefPubMed
Metadata
Title
Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors
Authors
Eirini Thanopoulou
Khin Thway
Komel Khabra
Ian Judson
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Clinical Sarcoma Research / Issue 1/2014
Electronic ISSN: 2045-3329
DOI
https://doi.org/10.1186/2045-3329-4-5

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