Journal of Clinical Oncology, Vol 15, 2604-2610, Copyright © 1997 by American Society of Clinical Oncology
Tumoral-reduced folates and clinical resistance to fluorouracil-based treatment in head and neck cancer patients
S Cheradame, MC Etienne, P Formento, M Schneider, O Dassonville, F Demard and G Milano
Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France.
PURPOSE: To describe the distribution of tumoral-reduced folates in cancer
patients and to analyze the link between this parameter and antitumor
efficacy of fluorouracil (FU)-based induction chemotherapy. PATIENTS AND
METHODS: Ninety-five patients with head and neck squamous cell carcinoma
were included in the present study and 41 received induction treatment with
FU-based chemotherapy (35 men and six women; mean age, 59 years; range, 40
to 76). Thymidylate synthase (TS) activity was measured according to the
tritium-release assay. Reduced folates (5-10 methylenetetrahydrofolate
[CH2FH4] plus tetrahydrofolate) were measured according to the entrapment
assay. RESULTS: Among the whole group of patients, reduced folates ranged
from nondetectable (< 0.3) to 17.7 pmol/mg protein; CH2FH4 ranged from
nondetectable (< 0.3) to 8.2 pmol/mg protein. There was no significant
link between tumoral levels of reduced folates and the severity of disease
stage. Among 41 treated patients, there were 12 (29%) complete responses
(CRs), 18 (44%) partial responses (PRs), and 11 patients (27%) with no
response (NR). No statistically significant relationship was observable
between TS activity and response. The distribution of CH2FH4 in tumors was
significantly higher for complete responders in comparison to patients with
a PR or NR. CONCLUSION: The present clinical data demonstrate the
importance of basal tumoral-reduced folates for the achievement of optimal
efficacy of FU-based treatment. They may have implications for the
identification of patients resistant to FU chemotherapy and for a better
understanding and management of FU modulation by folinic acid (FA).
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