title: Bevacizumab and everolimus in the treatment of patients with metastatic melanoma: a phase 2 trial of the Sarah Cannon Oncology Research Consortium.
abstract: BACKGROUND
  In this phase 2 study, the activity and tolerability of the combination of bevacizumab, an inhibitor of angiogenesis, and everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), was evaluated in the treatment of patients with metastatic melanoma.
  
  
  METHODS
  Patients with metastatic melanoma who had received up to 2 previous systemic regimens (chemotherapy and/or immunotherapy) were eligible. Previous treatment with angiogenesis or mTOR inhibitors was not allowed. All patients received bevacizumab at a dose of 15 mg/kg intravenously every 21 days and everolimus at a dose of 10 mg orally daily. Patients were re-evaluated every 6 weeks; those with an objective response or stable disease (according to Response Evaluation Criteria in Solid Tumors [RECIST]) continued therapy until tumor progression or unacceptable toxicity occurred.
  
  
  RESULTS
  Fifty-seven patients with metastatic melanoma received a median of 4 treatment cycles (range, 1-14+ cycles). Seven patients (12%) achieved major responses, whereas 33 patients (58%) were found to have stable disease at the time of first evaluation. The median progression-free and overall survivals were 4 months and 8.6 months, respectively. Approximately 43% of patients were alive after 12 months of follow-up. The treatment regimen was well tolerated by the majority of patients.
  
  
  CONCLUSIONS
  The combination of bevacizumab and everolimus was found to have moderate activity and was well tolerated in the treatment of patients with metastatic melanoma. Further exploration of agents with these mechanisms of action is indicated, perhaps in combination with inhibitors of the mitogen-activated protein kinase (MAPK) pathway.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. jhainsworth@tnonc.com
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: James D
authors.initials: JD
authors.lastname: Peyton
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Lane
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Clark
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rubin
authors.forename: David F
authors.initials: DF
authors.lastname: Trent
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000068338:Everolimus; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000068338:Everolimus; D020123:Sirolimus