title: Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sarina A
authors.initials: SA
authors.lastname: Piha-Paul
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Charles
authors.initials: C
authors.lastname: Levenback
authors.forename: Karen
authors.initials: K
authors.lastname: Lu
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D000068258:Bevacizumab; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013921:Thrombocytopenia / Q000139:chemically induced; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; C401859:temsirolimus; D001219:Aspartate Aminotransferases; D020123:Sirolimus
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