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), p53, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed on 82 advanced head and neck cancer patients (71 men, 11 women; mean age 59). Induction treatment was cisplatin-5-FU +/- folinic acid (61 patients, Chem group) or concomitant cisplatin-5-FU-radiotherapy (21 patients, RChem group). EGFR (binding assay), p53 protein (Sangtec immunoluminometric assay), TS and DPD activities (radioenzymatic assays) were measured on biopsies obtained at time of diagnosis. Significant positive correlation was demonstrated between p53 and EGFR. In the RChem group, p53 was higher in non-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)); survival increased when EGFR and p53 were below thresholds. Multivariate stepwise analysis including T staging, EGFR and p53 revealed that T staging and EGFR were independent predictors of survival; relative risks were 3.68 for T staging and 2.65 for EGFR. Overall, EGFR remained an independent prognostic factor when response to treatment and T staging were considered in the multivariate analysis.
Etienne
M C
MC
Centre Antoine Lacassagne, Nice, France.
Pivot
X
X
Formento
J L
JL
Bensadoun
R J
RJ
Formento
P
P
Dassonville
O
O
Francoual
M
M
Poissonnet
G
G
Fontana
X
X
Schneider
M
M
Demard
F
F
Milano
G
G
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D042943:Dihydrouracil Dehydrogenase (NADP); D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D066246:ErbB Receptors; D005472:Fluorouracil