Does cisplatin (CDDP) function as a modulator of 5-fluorouracil (5-FU) antitumor action? A study based on a clinical trial.
OBJECTIVE
To clarify whether CDDP acts as a modulator of 5-FU antitumor action in gastric cancer, patients were treated preoperatively with 5-FU + CDDP (FP) chemotherapy.


METHODS
From September 2000 to November 2001 at Takarazuka Municipal Hospital, 29 patients preoperatively diagnosed with stages II-IV gastric cancer were enrolled. Written informed consent was obtained from all patients. The patients were randomly assigned to two groups: the FU group, in which patients received a continuous intravenous infusion of 5-FU 320 mg/m2 per day over 24 h a day for 5 days beginning 5 days prior to surgery, and the FP group, in which patients received bolus intravenous injections of CDDP 3.5 mg/m2 per day for 5 days prior to surgery in addition to the same infusion of 5-FU as the FU group. As indicators of the intracellular effect of 5-FU treatment, thymidylate synthase (TS) inhibition rates, TS protein levels, TS and dihydropyrimidine dehydrogenase (DPD) activity, and F-RNA concentrations were measured.


RESULTS
Using Scheffe's multiple comparison test, in both treatment groups the tumor regions were found to have significantly higher TS inhibition rates than the nontumor regions (P<0.05). No significant differences in TS protein levels, TS activity, DPD activity or F-RNA concentrations were found between the four regions.


CONCLUSIONS
Our results show that CDDP clinically may act to enhance the antitumor effects of 5-FU in terms of the inhibition of DNA synthesis and could therefore act as a modulator of 5-FU.
Matsusaka
Satoshi
S
Department of Surgery, Sano Hospital, Simizugaoka 2-5-1, Tarumi-ku, Kobe, Hyogo, 655-0031, Japan. matsusaka-s@med.id.yamagata-u.ac.jp.|Department of Hygiene and Preventive Medicine, School of Medicine, Yamagata University, Iida-Nishi 2-2-2, Yamagata, 990-9585, Japan. matsusaka-s@med.id.yamagata-u.ac.jp.
Nagareda
Tomofumi
T
Department of Pathology, Takarazuka Municipal Hospital, Kohama 4-5-1, Takarazuka, Hyogo, 665-0827, Japan.
Yamasaki
Hajime
H
Department of Surgery, Takarazuka Municipal Hospital, Kohama 4-5-1, Takarazuka, Hyogo, 665-0827, Japan.
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013940:Thymidylate Synthase / Q000378:metabolism
D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil