[Effect of pylorus-preserving pancreaticoduodenectomy on serum levels of 5-fluorouracil during S-1 treatment for pancreaticobiliary malignancy].
OBJECTIVE
The aim of this study was to evaluate the effect of surgical procedures on the serum levels of 5-fluorouracil (5-FU) in patients undergoing S-1 treatment for pancreaticobiliary malignancy.


METHODS
From January 2003 through December 2008, 27 chemotherapy-naive patients who underwent a surgical procedure for pancreaticobiliary malignancy received S-1 chemotherapy for unresectable or recurrent disease. The primary site of disease was: the extra hepatic bile duct (n=10); gallbladder (n=8); pancreas (n=6); or ampulla of Vater (n=3). The surgical procedure was: pylorus-preserving pancreaticoduodenectomy (PPPD) (n=6); combined major hepatic and bile duct resection (n=6); bilioenteric anastomosis (n=4); or exploratory laparotomy (n=11). S-1 (80-120 mg/day) was administered orally twice daily for 28 days, followed by 14 days without therapy. Subsequently, the serum levels of 5-FU were measured using the HPLC-UV method.


RESULTS
The median number of cycles administered per patient was 6 (range, 2-13). Although grade 3 watery eye developed in one patient, neither grade 4 toxicities nor treatment-related deaths were observed. The overall response rate was 19%, the median overall survival time was 9 months, and the 1-year cumulative survival rate was 11%. The maximum levels of 5-FU in the sera of individual patients differed significantly according to the surgical procedure (Kruskal-Wallis test; p=0. 0049); the patients who underwent PPPD had the highest 5-FU levels, as compared with the other patients (Mann-Whitney test; p= 0.003).


CONCLUSIONS
The type of operative procedure appears to influence the serum levels of 5-FU in S-1-treated surgical patients with pancreaticobiliary malignancy. Given the possibility of elevated levels of 5-FU in the sera of patients who are treated with S-1 after PPPD, adverse events must be monitored carefully in this cohort.
Muneoka
Katsuki
K
Dept. of Surgery, Niitsu Medical Center Hospital.
Shirai
Yoshio
Y
Sasaki
Masataka
M
Wakai
Toshifumi
T
Sakata
Jun
J
Kanda
Junkichi
J
Wakabayashi
Hiroyuki
H
Hatakeyama
Katsuyoshi
K
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D016577:Pancreaticoduodenectomy / Q000379:methods*; D005641:Tegafur / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil