title: Efficacy and comparative effectiveness of sirolimus as an anticancer drug.
abstract: OBJECTIVE
  To evaluate antitumor efficacy of the generic mammalian target of rapamycin (mTOR) inhibitor sirolimus in preclinical animal models of head and neck squamous cell carcinoma (HNSCC) and compare its effects with those of the patented analogue temsirolimus.
  
  
  METHODS
  In vivo study.
  
  
  METHODS
  To develop xenograft established tumor model (ETM) of HNSCC, FaDu cells were injected subcutaneously into nude mice. When tumors reached 50 to 60 mm(3), mice were randomized into five groups and treated daily intraperitoneally with sirolimus at various doses for 5 days per week for 3 weeks. Tumor volumes were measured. The results were compared with historical data on temsirolimus effects. In the minimal residual disease (MRD) model, surgical wounds were created and FaDu cells implanted. After 72 hours, animals were randomized into two groups and were injected intraperitoneally with 0 or 5 mg/kg sirolimus for 5 days per week for 30 days.
  
  
  RESULTS
  In the ETM, sirolimus significantly inhibited tumor growth (P < .01), although there was no overall significant difference in tumor growth inhibition between sirolimus and temsirolimus. In the MRD model, sirolimus significantly suppressed growth of tumors (P < .001) and improved survival compared with controls (P < .01). There was a significant decrease in pS6 expression, indicating mTOR inhibition.
  
  
  CONCLUSIONS
  In this study, we demonstrate that the generic mTOR inhibitor sirolimus shows potent antitumor activity in HNSCC and produces comparable effects to the patent drug temsirolimus. Sirolimus has the potential of serving as an economic and comparative targeted agent to temsirolimus in the treatment of HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hu
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Ekshyyan
authors.forename: Lilantha
authors.initials: L
authors.lastname: Herman Ferdinandez
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Rong
authors.forename: Gloria
authors.initials: G
authors.lastname: Caldito
authors.forename: Cherie-Ann O
authors.initials: CO
authors.lastname: Nathan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000601:surgery*; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000601:surgery*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus