[Correlative analysis between serum dihydropyrimidine dehydrogenase, activity, concentration of 5-fluorouracil and adverse events in the treatment of advanced gastric cancer patients].
OBJECTIVE
Toxicities and their severities vary among advanced gastric cancer patients when they receive the same regimen containing continuous infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the key rate-limiting enzymes which is closely related to toxicities of 5-FU in chemotherapy. This study was to explore the relationship between activity of DPD and concentration of 5-FU, and their correlation to adverse events among advanced gastric cancer patients treated with the same regimen containing 5-FU continuous infusion.


METHODS
Patients received the same regimen (intravenous injection of paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was collected from 36 patients with advanced gastric cancer before and after chemotherapy to detect the activity of DPD and concentration of 5-FU by high-performance liquid chromatography (HPLC). Adverse events were assessed every cycle.


RESULTS
Serum activity of DPD revealed a unimodel distribution, which globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD activity values were 2.38 and 2.13, respectively. No total DPD deficiency was found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1 589.2 microg/L, which demonstrated normality distribution after a logarithmic transformation was applied. The DPD activity was inversely correlated with 5-FU concentration (r=-0.376, P=0.024). The patients with low activity of DPD were more frequently suffering from severe diarrhea, mucositis, and myelosuppression. And high level of 5-FU concentration led to the increase of adverse events.


CONCLUSIONS
Pre-chemotherapy DPD activity and 5-FU concentration during chemotherapy vary among gastric cancer patients, which may help to prevent severe toxicities during the treatment.
Peng
Rou-Jun
RJ
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Dong
Qiu-Mei
QM
Shi
Yan-Xia
YX
Cao
Ye
Y
Zhou
Zhong-Mei
ZM
Yuan
Zhong-Yu
ZY
Li
Su
S
Li
Hai
H
Jiang
Wen-Qi
WQ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000097:blood*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
D042943:Dihydrouracil Dehydrogenase (NADP); D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil