In collaboration with Dr J-F. Daisne (CHU UCL Namur)
Afatinib is an irreversible ErbB family blocker that potently inhibits signaling from all ErbB family receptor dimers formed by EGFR, HER2 and ErbB4. It inhibited cellular growth and induced apoptosis in several tumor cell lines including non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer and head and neck squamous cell cancer (HNSCC). Considering the interesting results of clinical trials in patients with EGFR mutation-positive NSCLC, afatinib was also investigated in head and neck squamous cell carcinoma (HNSCC) treatment. Indeed, EGFR is overexpressed in approximately 90% of HNSCC. Afatinib demonstrated clinical activity in a proof-of-concept phase II study in which this treatment was compared to cetuximab as a monotherapy in patients with platinum-refractory metastatic/recurrent HNSCC. Cisplatin-based chemoradiation is still the standard of care for definitive and adjuvant treatment of locoregionally advanced disease but until 30% of patients develop metastasis. Afatinib might have clinical benefit used in combination with cisplatin and radiotherapy. To our best knowledge, no study has shown the combined effects of afatinib and cisplatin with radiotherapy in HNSCC. Nevertheless, before initiating a clinical study, we have to determine the optimal duration of incubation with afatinib and/or cisplatin and the optimal timing of exposure to the drugs relative to irradiation in vitro and in murine tumor models.
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