Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study
Department of Obstetrics and Gynecology
Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Administration Schedule; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Megestrol Acetate; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Sirolimus; derivatives; Tamoxifen
Female Urogenital Diseases and Pregnancy Complications | Maternal and Child Health | Neoplasms | Obstetrics and Gynecology | Oncology | Women's Health
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.
Endometrial cancer, Hormonal therapy, Megestrol acetate, Tamoxifen, Temsirolimu
DOI of Published Version
Gynecol Oncol. 2014 Mar;132(3):585-92. doi: 10.1016/j.ygyno.2014.01.015. Epub 2014 Jan 20. Link to article on publisher's site
Fleming, Gini F.; Filiaci, Virginia L.; Marzullo, Brandon; Zaino, Richard J.; Davidson, Susan A.; Pearl, Michael; Makker, Vicky; Burke, James J. 2nd; Zweizig, Susan L.; Van Le, Linda; Hanjani, Parviz; Downey, Gordon; Walker, Joan L.; Reyes, Henry D.; and Leslie, Kimberly K., "Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study" (2014). Obstetrics and Gynecology Publications and Presentations. 117.