PMID- 16428506
OWN - NLM
STAT- MEDLINE
DCOM- 20060228
LR  - 20181203
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 12
IP  - 2
DP  - 2006 Jan 15
TI  - Cetuximab and irinotecan interact synergistically to inhibit the growth of 
      orthotopic anaplastic thyroid carcinoma xenografts in nude mice.
PG  - 600-7
AB  - PURPOSE: Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known 
      human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody 
      against epidermal growth factor receptor, offers new treatment potentials for 
      patient with ATC. Cetuximab has also been reported to have synergistic effects 
      when combined with irinotecan, a topoisomerase inhibitor. Therefore, we 
      hypothesized that cetuximab and irinotecan would be effective in inhibiting the 
      growth and progression of ATC in a murine orthotopic model. EXPERIMENTAL DESIGN: 
      The in vitro antiproliferative effects of cetuximab and irinotecan on ATC cell 
      line ARO were examined. We also studied the in vivo effects of cetuximab and 
      irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in 
      nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was 
      also compared with that of doxorubicin. RESULTS: Cetuximab alone did not show any 
      antiproliferative or proapoptotic effect on this cell line. However, when 
      combined with irinotecan, cetuximab potentiated the in vitro antiproliferative 
      and proapoptotic effect of irinotecan. Cetuximab, irinotecan, and 
      cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition 
      of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal 
      invasion, and tumor microvessel density were also significantly decreased in 
      these treatment groups. Furthermore, the cetuximab/irinotecan combination was 
      significantly more effective than doxorubicin in inhibiting the growth of 
      orthotopic ATC xenografts. CONCLUSIONS: Combination therapy with 
      cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC 
      xenografts in nude mice. Given the lack of curative options for patients with 
      ATC, combination therapy with cetuximab and irinotecan treatment warrants further 
      study.
FAU - Kim, Seungwon
AU  - Kim S
AD  - Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Prichard, Christopher N
AU  - Prichard CN
FAU - Younes, Maher N
AU  - Younes MN
FAU - Yazici, Yasemin D
AU  - Yazici YD
FAU - Jasser, Samar A
AU  - Jasser SA
FAU - Bekele, B Nebiyou
AU  - Bekele BN
FAU - Myers, Jeffrey N
AU  - Myers JN
LA  - eng
GR  - P50 CA097007/CA/NCI NIH HHS/United States
GR  - P50 CA 97007A/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 7673326042 (Irinotecan)
RN  - PQX0D8J21J (Cetuximab)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Apoptosis/*drug effects
MH  - Camptothecin/administration & dosage/analogs & derivatives
MH  - Carcinoma/*drug therapy/metabolism/prevention & control
MH  - Cell Adhesion/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cetuximab
MH  - Drug Interactions
MH  - Drug Synergism
MH  - Humans
MH  - Irinotecan
MH  - Lymphatic Metastasis/prevention & control
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Survival Rate
MH  - Thyroid Neoplasms/*drug therapy/metabolism/prevention & control
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
PMC - PMC1403833
MID - NIHMS8641
EDAT- 2006/01/24 09:00
MHDA- 2006/03/01 09:00
PMCR- 2008/01/27
CRDT- 2006/01/24 09:00
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2006/03/01 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
PHST- 2008/01/27 00:00 [pmc-release]
AID - 12/2/600 [pii]
AID - 10.1158/1078-0432.CCR-05-1325 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2006 Jan 15;12(2):600-7. doi: 10.1158/1078-0432.CCR-05-1325.