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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 HN5 cell line-derived xenografts. Mice were treated daily with either vehicle (gray), 2 × 100 mg/kg/day lapatinib (turquoise), 75 mg/kg/day erlotinib (green), 50 mg/kg/day neratinib (blue), or 15 mg/kg/day afatinib (orange) as described in “Materials and methods.” Tumor volumes were recorded three times a week. Median tumor volumes were plotted over time (a). On day 50, relative tumor volume changes were recorded b
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Fig4: In vivo activity of afatinib in HN5 cell line-derived xenografts. Mice were treated daily with either vehicle (gray), 2 × 100 mg/kg/day lapatinib (turquoise), 75 mg/kg/day erlotinib (green), 50 mg/kg/day neratinib (blue), or 15 mg/kg/day afatinib (orange) as described in “Materials and methods.” Tumor volumes were recorded three times a week. Median tumor volumes were plotted over time (a). On day 50, relative tumor volume changes were recorded b

Mentions: The anti-tumor activity of afatinib and several other ErbB targeting agents was further tested in mice bearing HN5 xenografts (Fig. 4). Daily treatment at 15 mg/kg resulted in tumor regressions in all treated animals. Four complete responses and six responses displaying 75 % or more reduction in tumor size compared to baseline were observed. Erlotinib, at 75 mg/kg, was less potent and induced six regressions and four tumors grew under treatment. Neratinib and lapatinib induced tumor growth delay, but no regressions were achieved.Fig. 4


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 HN5 cell line-derived xenografts. Mice were treated daily with either vehicle (gray), 2 × 100 mg/kg/day lapatinib (turquoise), 75 mg/kg/day erlotinib (green), 50 mg/kg/day neratinib (blue), or 15 mg/kg/day afatinib (orange) as described in “Materials and methods.” Tumor volumes were recorded three times a week. Median tumor volumes were plotted over time (a). On day 50, relative tumor volume changes were recorded b
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Related In: Results  -  Collection

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Fig4: In vivo activity of afatinib in HN5 cell line-derived xenografts. Mice were treated daily with either vehicle (gray), 2 × 100 mg/kg/day lapatinib (turquoise), 75 mg/kg/day erlotinib (green), 50 mg/kg/day neratinib (blue), or 15 mg/kg/day afatinib (orange) as described in “Materials and methods.” Tumor volumes were recorded three times a week. Median tumor volumes were plotted over time (a). On day 50, relative tumor volume changes were recorded b
Mentions: The anti-tumor activity of afatinib and several other ErbB targeting agents was further tested in mice bearing HN5 xenografts (Fig. 4). Daily treatment at 15 mg/kg resulted in tumor regressions in all treated animals. Four complete responses and six responses displaying 75 % or more reduction in tumor size compared to baseline were observed. Erlotinib, at 75 mg/kg, was less potent and induced six regressions and four tumors grew under treatment. Neratinib and lapatinib induced tumor growth delay, but no regressions were achieved.Fig. 4

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