The ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase in tumour tissues of patients with metastatic gastric cancer is predictive of the clinical response to 5'-deoxy-5-fluorouridine.
The aim of this work was to determine whether intratumour contents of thymidine phosphorylase (TP), which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil, and dihydropyrimidine dehydrogenase (DPD), which degrades 5-fluorouracil to inactive molecules, could be useful in predicting the response of patients with metastatic gastric cancer to chemotherapy using 5'-DFUR. Endoscopic biopsy specimens for the measurement of TP and DPD were obtained from the primary lesions before the start of combination chemotherapy, in which 5'-DFUR, cisplatin and mitomycin C were administered. TP and DPD were measured by enzyme-linked immunosorbent assays after the objective responses to chemotherapy had been confirmed. Twenty five patients were enrolled in this study and data for 22 patients in whom responses were confirmed were analysed. The median levels (ranges) of TP and DPD were 80 (4.9-360) and 44 (15-82) U/mg protein, respectively. The median value (range) of TP to DPD ratios was 1.9 (0.25-5.1). Eight patients with a complete or partial response to chemotherapy had significantly higher TP to DPD ratios than did the remaining patients with stable or progressive disease (P = 0.014). When a cut-off level of TP to DPD ratio was defined as the median value, the high-ratio group (n = 11) showed a significantly higher response rate (64% vs. 9.1%, P = 0.024) than the low-ratio group (n = 11). Overall survival of the high-ratio group was significantly longer than that of the low-ratio group (the median survival time; 300 days vs. 183 days, P = 0.047). The efficacy of 5'-DFUR could be optimised by preselecting patients with high TP/ DPD ratios in their tumour tissues, and this would be applicable to the treatment with capecitabine.
Nishina
Tomohiro
T
Department of Medical Oncology, National Shikoku Cancer Center, 13 Horinouchi, Matsuyama, Ehime 790 0007, Japan. tnishina@shikoku-cc.go.jp
Hyodo
Ichinosuke
I
Miyaike
Jiro
J
Inaba
Tomoki
T
Suzuki
Seiyuu
S
Shiratori
Yasushi
Y
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000556:secondary*; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; C025034:doxifluridine