Oncotarget

Research Papers:

Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus

Sarina A. Piha-Paul _, Jennifer J. Wheler, Siqing Fu, Charles Levenback, Karen Lu, Gerald S. Falchook, Aung Naing, David S. Hong, Apostolia M. Tsimberidou and Razelle Kurzrock

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Oncotarget. 2014; 5:1846-1855. https://doi.org/10.18632/oncotarget.1834

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Abstract

Sarina A. Piha-Paul1, Jennifer J. Wheler1, Siqing Fu1, Charles Levenback2, Karen Lu2, Gerald S. Falchook1, Aung Naing1, David S. Hong1, Apostolia M. Tsimberidou1, Razelle Kurzrock3

1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, TX

2 Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX

3 Moores Cancer Center, The University of California San Diego, La Jolla, CA, U.S.A

Correspondence:

Sarina A. Piha-Paul, email:

Keywords: Gynecologic Malignancy, Bevacizumab, Temsirolimus

Received: January 31, 2014 Accepted: March 19, 2014 Published: March 20, 2014

Abstract

Background: Bevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1α 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.


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