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Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus. Oncotarget 2014 Apr 15;5(7):1846-55

Date

04/20/2014

Pubmed ID

24742900

Pubmed Central ID

PMC4039109

DOI

10.18632/oncotarget.1834

Scopus ID

2-s2.0-84899011208 (requires institutional sign-in at Scopus site)   30 Citations

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.

Author List

Piha-Paul SA, Wheler JJ, Fu S, Levenback C, Lu K, Falchook GS, Naing A, Hong DS, Tsimberidou AM, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Aspartate Aminotransferases
Bevacizumab
Carcinoma
Fatigue
Female
Humans
Hypercholesterolemia
Hypertension
Male
Middle Aged
Mucositis
Neutropenia
Ovarian Neoplasms
Sirolimus
Thrombocytopenia
Uterine Cervical Neoplasms