Cetuximab Plus Radiotherapy For Head And Neck CancerPresentation Transcript
Cetuximab plus Radiotherapy for Head and Neck Cancer Rena Callahan Journal Club UCLA Internal Medicine Faculty Discussant: Steven Wong
Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck Bonner JA; Harari PM; Giralt J; Azarnia N; Shin DM; Cohen RB; Jones CU; Sur R; Raben D; Jassem J; Ove R; Kies MS; Baselga J; Youssoufian H; Amellal N; Rowinsky EK; Ang KK N Engl J Med. 2006 Feb 9 Volume 354(6):567-78.
Head and Neck Cancer
The role of EGFR
Head and Neck Cancer (HNC)
40,000 cases annually in U.S.
>60% locoregionally advanced
Increased Risk: Tobacco and ETOH
Head and Neck Anatomy
Cell surface growth regulator expressed by two-thirds of all human cancer cells
Upregulated in 98% of HNC
EGFR expression has prognostic significance
Recombinant human/mouse chimeric Monoclonal antibody vs EGFR
Binds EGFR, HER1, c-ErbB-1 on both normal and tumor cells
Blocks EGF and other ligand binding
Binding to the EGFR blocks phosphorylation and activation of receptor-associated kinases
Inhibits cell growth, induction of apoptosis, and decreases matrix metalloproteinase and vascular endothelial growth factor production.
Cetuximab Adverse Events
acneform skin rash
The Approval of Cetuximab
Treatment – Locally Advanced HNC
5-yr survival 10-30%
Chemo and Radiation vs.
Increased Survival (Brizel 1998, Wendt 1998, Calais 1999, Budach 2006)
Severe mucositis 71% vs 39% (Calais 1999)
Short doubling times in HNC
Same dose over shorter time
Goal=prevent tumor repopulation
Multiple, smaller doses, daily
Increased total dose
mucositis, odynophagia, dysphagia, hoarseness, xerostomia, dermatitis, and weight loss
Which agents are the best to combine with radiation?
What is the role of adding targeted therapies?
Is combination chemotherapy better than single-agent chemotherapy?
Is altered fractionation better than conventional fractionation with CRT?
Does induction chemotherapy provide additional benefit?
Discussion- Cancer therapy trials
Difficulty with true control arms
Difficulty with blinding
When the “gold standard” keeps changing
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