Gini F Fleming1, Virginia L Filiaci2, Brandon Marzullo2, Richard J Zaino3, Susan A Davidson4, Michael Pearl5, Vicky Makker6, James J Burke7, Susan L Zweizig8, Linda Van Le9, Parviz Hanjani10, Gordon Downey11, Joan L Walker12, Henry D Reyes13, Kimberly K Leslie13. 1. University of Chicago, Chicago, IL 60637, United States. Electronic address: gfleming@medicine.bsd.uchicago.edu. 2. Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. 3. Hershey Medical Center, Medical Center of Pennsylvania State University, Hershey, PA 17033, United States. 4. University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, CO 80045, United States. 5. Stony Brook University Hospital, Stony Brook, NY 11794, United States. 6. Memorial Sloan-Kettering Cancer Center, New York, NY 10021, United States. 7. Memorial Medical Center, Savannah, GA 31404, United States. 8. UMass Memorial Medical Center, Worcester, MA 01605, United States. 9. UNC-Chapel Hill, Chapel Hill, NC 27599, United States. 10. Hanjani Institute for Gynecologic Oncology, Abington, PA 19001, United States. 11. Gynecologic Oncology of West Michigan, Grand Rapids, MI 49546, United States. 12. University of Oklahoma, Oklahoma City, OK 73190, United States. 13. University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States.
Abstract
OBJECTIVES: 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. BACKGROUND: Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. METHODS: We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
OBJECTIVES: 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. BACKGROUND: Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. METHODS: We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. RESULTS: 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. CONCLUSIONS: 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.
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