Clinical relevance of thymidylate synthase (TS) activity for S-1-based chemotherapy in squamous cell carcinoma of the oral cavity

Abstract S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA biosynthetic pathway, and improves clinical response...

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Bibliographic Details
Published in:British journal of oral & maxillofacial surgery 2010-03, Vol.48 (2), p.88-93
Main Authors: Koga, Makoto, Anegawa, Emiko, Yoh, Junko, Tsuyama, Haruki, Sakaino, Hidenori, Iwamoto, Osamu, Koga, Chihiro, Kusukawa, Jingo
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic - therapeutic use
Biological and medical sciences
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - enzymology
Dentistry
Dermatology
Drug Administration Schedule
Drug Combinations
Enzyme-Linked Immunosorbent Assay
Female
Humans
Kaplan-Meier Estimate
Male
Medical sciences
Middle Aged
Mouth Neoplasms - drug therapy
Mouth Neoplasms - enzymology
Oral cancer
Otorhinolaryngology. Stomatology
Oxonic Acid - therapeutic use
Prognosis
Retrospective Studies
S-1
Squamous cell carcinoma
Statistics, Nonparametric
Surgery
Tegafur - therapeutic use
Thymidylate synthase
Thymidylate Synthase - metabolism
Tumors of the skin and soft tissue. Premalignant lesions
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Summary:Abstract S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA biosynthetic pathway, and improves clinical response to chemotherapy with fluoropyrimidines. We have retrospectively evaluated the predictive value of thymidylate synthase activity in 75 patients with oral SCC with an enzyme-linked immunosorbent assay (ELISA). Mean (SD) activity (pmol/mg) in the specimens was 0.078 (0.080) (median 0.059). The median value was taken as the cut-off value based on which the patients were divided into high and low activity groups. Both the clinical and histopathological responses to chemotherapy and radiochemotherapy were higher in the group with low TS activity. The group with low TS activity also differed significantly in their clinical response to S-1-based chemotherapy ( p < 0.05). However, there was no significant difference in cause-specific survival. Measurement of TS activity may aid in predicting the clinical response to chemotherapy including S-1 for oral SCC.
ISSN:0266-4356
1532-1940
DOI:10.1016/j.bjoms.2009.05.010