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Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Young NR, Soneru C, Liu J, Grushko TA, Hardeman A, Olopade OI, Baum A, Solca F, Cohen EE - Target Oncol (2015)

Bottom Line: Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib.Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo.Both afatinib and cetuximab were effective in tumor xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Comprehensive Cancer Center, University of Chicago, 900 E. 57th Street, Chicago, IL, 60637, USA. natyoung@bsd.uchicago.edu.

ABSTRACT
Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification.

No MeSH data available.


Related in: MedlinePlus

In vivo activity of afatinib in FaDu cell line-derived xenografts. Mice were treated daily with either vehicle (black circle) or afatinib as described in (white triangle) or in a weekly alternating schedule (white square). Tumor volumes and body weights were recorded three times a week, and median tumor volumes (a) as well as change in body weight (b) were plotted over time
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Fig3: In vivo activity of afatinib in FaDu cell line-derived xenografts. Mice were treated daily with either vehicle (black circle) or afatinib as described in (white triangle) or in a weekly alternating schedule (white square). Tumor volumes and body weights were recorded three times a week, and median tumor volumes (a) as well as change in body weight (b) were plotted over time

Mentions: In vivo activity of afatinib was first characterized against FaDu cells injected into the right flank of BomTac:NMRI-Foxn1nu mice. Treatment with afatinib at 10 mg/kg followed two regimens. Both daily and intermittent treatment regimens slowed tumor growth. Continuous dosing resulted in virtually no tumor growth, while intermittent dosing saw increase in tumor volume over time (Fig. 3a). Neither treatment regimen at the doses used had a significant effect on body weight (Fig. 3b).Fig. 3


Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Young NR, Soneru C, Liu J, Grushko TA, Hardeman A, Olopade OI, Baum A, Solca F, Cohen EE - Target Oncol (2015)

In vivo activity of afatinib in FaDu cell line-derived xenografts. Mice were treated daily with either vehicle (black circle) or afatinib as described in (white triangle) or in a weekly alternating schedule (white square). Tumor volumes and body weights were recorded three times a week, and median tumor volumes (a) as well as change in body weight (b) were plotted over time
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492891&req=5

Fig3: In vivo activity of afatinib in FaDu cell line-derived xenografts. Mice were treated daily with either vehicle (black circle) or afatinib as described in (white triangle) or in a weekly alternating schedule (white square). Tumor volumes and body weights were recorded three times a week, and median tumor volumes (a) as well as change in body weight (b) were plotted over time
Mentions: In vivo activity of afatinib was first characterized against FaDu cells injected into the right flank of BomTac:NMRI-Foxn1nu mice. Treatment with afatinib at 10 mg/kg followed two regimens. Both daily and intermittent treatment regimens slowed tumor growth. Continuous dosing resulted in virtually no tumor growth, while intermittent dosing saw increase in tumor volume over time (Fig. 3a). Neither treatment regimen at the doses used had a significant effect on body weight (Fig. 3b).Fig. 3

Bottom Line: Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib.Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo.Both afatinib and cetuximab were effective in tumor xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Comprehensive Cancer Center, University of Chicago, 900 E. 57th Street, Chicago, IL, 60637, USA. natyoung@bsd.uchicago.edu.

ABSTRACT
Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification.

No MeSH data available.


Related in: MedlinePlus