title: A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC.
  
  
  METHODS
  A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle.
  
  
  RESULTS
  Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively.
  
  
  CONCLUSIONS
  This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.
authors.affiliation: Staff Medical Oncologist, Gastrointestinal Oncology Lead, Princess Margaret Cancer Centre, University of Toronto, 5-210, 610 University Ave, Toronto, ON, M5G 2 M9, USA, jennifer.knox@uhn.ca.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Strosberg
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tan
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaubisch
authors.forename: Anthony B
authors.initials: AB
authors.lastname: El-Khoueiry
authors.forename: Tanios S
authors.initials: TS
authors.lastname: Bekaii-Saab
authors.forename: Steven R
authors.initials: SR
authors.lastname: Rousey
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D000068258:Bevacizumab; C401859:temsirolimus; D020123:Sirolimus