[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].
We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.
Kotake
K
K
Dept. of Surgery, Tochigi Cancer Center, Utsunomiya, Japan.
Koyama
Y
Y
Konishi
F
F
Kanazawa
K
K
Namba
M
M
Shida
S
S
Umemoto
S
S
Nara
K
K
Kon
T
T
Nozawa
K
K
D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000032:analysis*; D006801:Humans; D008297:Male; D012004:Rectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013488:Suppositories; D005641:Tegafur / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D013488:Suppositories; D005641:Tegafur; D013940:Thymidylate Synthase; D005472:Fluorouracil