[Relationship of serum level of dihydropyrimidine dehydrogenase and serum concentration of 5-fluorouracil to treatment response and adverse events in colorectal cancer patients].
OBJECTIVE
Toxicities and response are different when patients with advanced colorectal cancer were treated with standard FOLFOX6 regimen. Serum level of dihydropyrimidine dehydrogenase (DPD) relates to efficacy and toxicities of chemotherapy containing 5-fluorouracil (5-FU). This study was to explore relationship of DPD to serum concentration of 5-FU in colorectal cancer patients treated with FOLFOX6 regimen, and their correlation to treatment response and adverse events.


METHODS
Serum level of DPD in 72 patients with colorectal cancer was detected by high-performance liquid chromatography (HPLC) before chemotherapy. Serum concentration of 5-FU at steady state was detected by HPLC after patients received FOLFOX6 regimen. Treatment response and adverse events in the patients were assessed.


RESULTS
Serum levels of DPD were normally distributed in 72 patients (ranged 1.55-5.94), while serum concentrations of 5-FU at steady state were not (ranged 141.1-1 741.9 microg/L). Serum level of DPD was negatively correlated with serum concentration of 5-FU (r=-0.460, P < 0.01). Occurrence of adverse events was lower when 5-FU concentration was less than 600 microg/L than when 5-FU concentration was more than 600 microg/L (P < 0.05). The mean serum concentration of 5-FU was significantly higher in patients with complete response and partial response than in patients with steady disease, and progressive disease (513.9 microg/L vs. 409.8 microg/L, and 259.3 microg/L, P < 0.05). Serum level of DPD was lower in patients suffered oral mucositis and diarrhea of grade II-IV than in patients suffered oral mucositis and diarrhea of grade 0-I (P=0.016, P=0.047). Serum level of DPD had no relation with treatment response of the patients (r=0.312, P=0.078).


CONCLUSIONS
DPD level and serum 5-FU concentration vary a lot among patients with colorectal cancer. DPD level negatively correlates with serum 5-FU concentration. Serum concentration of 5-FU correlates with treatment effect and toxicities.
Dong
Qiu-Mei
QM
Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China. dqmzhang@163.com
He
You-Jian
YJ
Li
Su
S
Zhou
Zhong-Mei
ZM
Zhang
Li
L
Zhou
Zhi-Wei
ZW
Xia
Zhong-Jun
ZJ
Li
Yu-Yan
YY
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D003967:Diarrhea / Q000139:chemically induced; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000097:blood*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology
D009944:Organoplatinum Compounds; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil