A multifactorial approach including tumoural epidermal growth factor receptor, p53, thymidylate synthase and dihydropyrimidine dehydrogenase to predict treatment outcome in head and neck cancer patients receiving 5-fluorouracil

The prognostic value of tumoural epidermal growth factor receptor (EGFR), p 53, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed on 82 advanced head and neck cancer patients (71 men, 11 women; m ean age 59). induction treatment was cisplatin-5-FU +/- folinic acid (61 pa tients, Chem group) or concomitant cisplatin-5-FU-radiotherapy (21 patients , RChem group). EGFR (binding assay), p53 protein (Sangtec immunoluminometr ic assay), TS and DPD activities (radioenzymatic assays) were measured on b iopsies obtained at time of diagnosis. Significant positive correlation was demonstrated between p53 and EGFR. In the RChem group, p53 was higher in n on-complete responders (median 1.03 ng mg(-1)) than in complete responders (median 0.08 ng mg(-1)) (P = 0.057). Univariate Cox analyses stratified on treatment group showed that specific survival (33 events) was significantly related to T staging, p53 taken as continuous or categorial (below vs over 0.80 ng mg(-1)) variable, and EGFR (below vs over 220 fmol mg(-1)); surviv al increased when EGFR and p53 were below thresholds. Multivariate stepwise analysis including T staging, EGFR and p53 revealed that T staging and EGF R were independent predictors of survival; relative risks were 3.68 for T s taging and 2.65 for EGFR. Overall, EGFR remained an independent prognostic factor when response to treatment and T staging were considered in the mult ivariate analysis.