PMID- 21520111
OWN - NLM
STAT- MEDLINE
DCOM- 20110628
LR  - 20211020
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 121
IP  - 5
DP  - 2011 May
TI  - Efficacy and comparative effectiveness of sirolimus as an anticancer drug.
PG  - 978-82
LID - 10.1002/lary.21724 [doi]
AB  - OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: 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.
CI  - Copyright (c) 2011 The American Laryngological, Rhinological, and Otological 
      Society, Inc.
FAU - Hu, Melissa
AU  - Hu M
AD  - Department of Otolaryngology-Head and Neck Surgery, Louisiana State University 
      Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
FAU - Ekshyyan, Oleksandr
AU  - Ekshyyan O
FAU - Herman Ferdinandez, Lilantha
AU  - Herman Ferdinandez L
FAU - Rong, Xiaohua
AU  - Rong X
FAU - Caldito, Gloria
AU  - Caldito G
FAU - Nathan, Cherie-Ann O
AU  - Nathan CO
LA  - eng
GR  - R01 CA102363/CA/NCI NIH HHS/United States
GR  - R01 CA102363-05S1/CA/NCI NIH HHS/United States
GR  - R01CA102363/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Antineoplastic Agents)
RN  - 624KN6GM2T (temsirolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Squamous Cell/*surgery
MH  - Disease Models, Animal
MH  - Head and Neck Neoplasms/*surgery
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Sirolimus/*analogs & derivatives/*therapeutic use
PMC - PMC3085006
MID - NIHMS264479
COIS- Conflict of Interest: None
EDAT- 2011/04/27 06:00
MHDA- 2011/06/29 06:00
PMCR- 2012/05/01
CRDT- 2011/04/27 06:00
PHST- 2011/04/27 06:00 [entrez]
PHST- 2011/04/27 06:00 [pubmed]
PHST- 2011/06/29 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - 10.1002/lary.21724 [doi]
PST - ppublish
SO  - Laryngoscope. 2011 May;121(5):978-82. doi: 10.1002/lary.21724.