Docetaxel (T), cisplatin (P), and TP 5-fluorouracil (F) with or without cetuximab in head and neck squamous cell carcinoma (HNSCC): Simulation of ex vivo results in the FLAVINO-assay.

e16016 Background: Individual response evaluation in head and neck squamous cell carcinomas (HNSCC) would be welcome for better biology-based decision making since therapy strategies like concurrent radio-chemo and induction-chemo (IC) compete with surgery e.g. of resectable advanced HNSCC. However, inter-individual differences in response to mixtures of chemotherapeutics and biologicals are not exactly known even in guideline-conform treatments. The purpose was to analyze combined effects of T, P, F, and cetuximab (E) on colony formation (CF) of HNSCC in the FLAVINO assay and the comparison with the clinical response to IC. Methods: Before starting IC, biopsies were taken, collagenase-digested and exposed to T and/or P at quarter, half, and exact their tolerable plasma (TPL) levels (6.6 and 0.55 µM) in presence or absence of F (1.5 µM)±E, and controls. To facilitate counting of colonies formed within 72h, epithelial cells were stained by Cy2-labeled pan-cytokeratin antibodies. The 28-d response to the first cycle of IC (reduction in surface and volume of the primary) was compared with CF. Results: Poorest response to IC was observed in patients with HNSCC unable to form epithelial colonies (13/36). Of the 63.9% ex vivo growing HNSCC, 34.8% (8/23) and 8.7% (2/27) responded to C and T in concentrations ≤TPL with completely inhibited CF. This rate was increased in presence of E. 22/23 (95.6%) HNSCC formed >4 epithelial colonies and allowed for IC50 calculation. TP+E and TPF+E proved to be more effective than binary combinations. Combined with increasing doses of P, the IC50 of T decreased and indicated superiority compared to treatment with T in binary combination with F. We found a high correlation of ex vivo and in vivo response of HNSCC. Conclusions: Complete suppression of CF and failure to form colonies ex vivo best predicted responsiveness or resistance to IC. Despite mostly additive or synergistic effects of TP and TPF ex vivo, identification of HNSCC probably failing to benefit from IC prior to starting therapy could reduce the risk of choosing inappropriate treatment modalities for HNSCC.