Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study

Gini F Fleming; Virginia L Filiaci; Brandon Marzullo; Richard J Zaino; Susan A Davidson; Michael Pearl; Vicky Makker; James J Burke; Susan L Zweizig; Linda Van Le; Parviz Hanjani; Gordon Downey; Joan L Walker; Henry D Reyes; Kimberly K Leslie

doi:10.1016/j.ygyno.2014.01.015

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Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study

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Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study

Gini F Fleming, Virginia L Filiaci, Brandon Marzullo, Richard J Zaino, Susan A Davidson, Michael Pearl, Vicky Makker, James J Burke, Susan L Zweizig, Linda Van Le, …

Gynecologic Oncology, Vol.132(3), pp.585-592

03/2014

DOI: 10.1016/j.ygyno.2014.01.015

PMCID: PMC4063288

PMID: 24456823

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Abstract

To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma. Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single agent arm with 3 episodes of DVT and 11 responses (22%). Response rates were similar in patients with prior chemotherapy (7 of 29; 24%) and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with clear cell carcinoma responded. Adding the combination of megestrol acetate and tamoxifen to temsirolimus therapy did not enhance activity and the combination was associated with an excess of venous thrombosis. Temsirolimus activity was preserved in patients with prior adjuvant chemotherapy. •The combination of hormone therapy plus temsirolimus did not improve response rates compared to temsirolimus alone.•The combination of therapy with megestrol acetate/tamoxifen plus temsirolimus resulted in a 33% rate of venous thrombosis.•Two of four patients with clear cell carcinoma of the endometrium responded to temsirolimus.

Temsirolimus

Megestrol acetate

Endometrial cancer

Tamoxifen

Hormonal therapy

Details

Title: Subtitle: Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study
Creators: Gini F Fleming - University of Chicago, Chicago, IL 60637, United States
Virginia L Filiaci - Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Brandon Marzullo - Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Richard J Zaino - Hershey Medical Center, Medical Center of Pennsylvania State University, Hershey, PA 17033, United States
Susan A Davidson - University of Colorado Cancer Center — Anschutz Cancer Pavilion, Aurora, CO 80045, United States
Michael Pearl - Stony Brook University Hospital, Stony Brook, NY 11794, United States
Vicky Makker - Memorial Sloan–Kettering Cancer Center, New York, NY 10021, United States
James J Burke - Memorial Medical Center, Savannah, GA 31404, United States
Susan L Zweizig - UMass Memorial Medical Center, Worcester, MA 01605, United States
Linda Van Le - UNC-Chapel Hill, Chapel Hill, NC 27599, United States
Parviz Hanjani - Hanjani Institute for Gynecologic Oncology, Abington, PA 19001, United States
Gordon Downey - Gynecologic Oncology of West Michigan, Grand Rapids, MI 49546, United States
Joan L Walker - University of Oklahoma, Oklahoma City, OK 73190, United States
Henry D Reyes - University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
Kimberly K Leslie - University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Gynecologic Oncology, Vol.132(3), pp.585-592
DOI: 10.1016/j.ygyno.2014.01.015
PMID: 24456823
PMCID: PMC4063288
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute, award: CA 27469, CA 37517
Language: English
Date published: 03/2014
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983930274302771

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