TY - JOUR
T1 - Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus
AU - Piha-Paul, Sarina A.
AU - Wheler, Jennifer J.
AU - Fu, Siqing
AU - Levenback, Charles
AU - Lu, Karen
AU - Falchook, Gerald S.
AU - Naing, Aung
AU - Hong, David S.
AU - Tsimberidou, Apostolia M.
AU - Kurzrock, Razelle
PY - 2014
Y1 - 2014
N2 - Background: Bevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1a levels, a resistance mechanism for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant in these tumors Patients and Methods: We analyzed safety and responses in 41 patients with gynecologic cancers treated as part of a Phase I study of bevacizumab and temsirolimus. Results: Median age of the 41 women was 60 years (range, 33-80 years); median number of prior systemic therapies was 4 (1-11). Grade 3 or 4 treatment-related toxicities included: thrombocytopenia (10%), mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%), elevated aspartate aminotransferase (2%), and neutropenia (2%). Twenty-nine patients (71%) experienced no treatment-related toxicity greater than grade 2. Full FDA-approved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25mg IV weekly) were administered without dose-limiting toxicity. Eight patients (20%) achieved stable disease (SD) ≥ 6 months and 7 patients (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13 patients (62%) with high-grade serous histology (ovarian or primary peritoneal) achieved SD ≥ 6 months/PR. Conclusion: Bevacizumab and temsirolimus was well tolerated. Thirty-seven percent of heavily-pretreated patients achieved SD ≥6 months/PR, suggesting that this combination warrants further study.
AB - Background: Bevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1a levels, a resistance mechanism for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant in these tumors Patients and Methods: We analyzed safety and responses in 41 patients with gynecologic cancers treated as part of a Phase I study of bevacizumab and temsirolimus. Results: Median age of the 41 women was 60 years (range, 33-80 years); median number of prior systemic therapies was 4 (1-11). Grade 3 or 4 treatment-related toxicities included: thrombocytopenia (10%), mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%), elevated aspartate aminotransferase (2%), and neutropenia (2%). Twenty-nine patients (71%) experienced no treatment-related toxicity greater than grade 2. Full FDA-approved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25mg IV weekly) were administered without dose-limiting toxicity. Eight patients (20%) achieved stable disease (SD) ≥ 6 months and 7 patients (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13 patients (62%) with high-grade serous histology (ovarian or primary peritoneal) achieved SD ≥ 6 months/PR. Conclusion: Bevacizumab and temsirolimus was well tolerated. Thirty-seven percent of heavily-pretreated patients achieved SD ≥6 months/PR, suggesting that this combination warrants further study.
KW - Bevacizumab
KW - Gynecologic malignancy
KW - Temsirolimus
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UR - http://www.scopus.com/inward/citedby.url?scp=84899011208&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.1834
DO - 10.18632/oncotarget.1834
M3 - Article
C2 - 24742900
AN - SCOPUS:84899011208
SN - 1949-2553
VL - 5
SP - 1846
EP - 1855
JO - Oncotarget
JF - Oncotarget
IS - 7
ER -