[Results of prophylactic hepatic arterial chemotherapy for liver metastases of Dukes C colorectal cancer--correlation with tumoral expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53, or orotate phosphoribosyl transferase].
The purpose of this study was (1) to disclose data from a non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from Dukes'C colorectal cancer, (2) to examine the influence of the expression of dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), and p53 in the primary lesion on this chemotherapy, and (3) to examine the expression of orotate phosphoribosyl transferase (OPRT) mRNA levels in the cases of recurrence included in this study. Patients who underwent curative resection of Dukes'C colorectal cancer between November 1996 and April 2000 were examined. After curative resection, patients were non-randomly divided into two groups after obtaining their informed consent: Hepatic arterial infusion (HAI) group patients (n = 28) were given 5-FU (500 mg/body for 1 h per week, repeated 50 times) via the hepatic artery and peroral UFT-E after resection of Dukes'C colorectal cancer. Control group patients (n = 21) received UFT-E alone. Liver metastasis-free survival did not differ between the groups. Immunohistochemical examinations revealed that the expression of tumoral DPD or p53 was unlikely to affect the hepatic recurrence, although patients with a low expression of TS tended to have better survival in both groups. However, multivariate analysis by the Cox proportional hazard model revealed that a significant prognostic factor influencing the hepatic recurrence is extensive venous invasion. Expression levels of OPRT mRNA, measured in tumors of patients with recurrence (n = 6 for the HAI group; and n = 4 for the control group) were not significantly different between the groups. These results suggest that (1) intermittent hepatic arterial infusion of 5-FU in addition to oral UFT-E was not more useful than administration of UFT alone, and (2) the expression of DPD, TS, p53, and OPRT in the primary lesion was unlikely to affect the prognosis of patients included in this study.
Ishida
Hideyuki
H
Dept. of Surgery, Saitama Medical School.
Yamada
Hirofumi
H
Shirakawa
Kazuo
K
Nakada
Hiroshi
H
Ohsawa
Tomonori
T
Takeuchi
Ikuya
I
Okada
Norimichi
N
Yokoyama
Masaru
M
Inokuma
Shigehisa
S
Suzuki
Tsuyoshi
T
Odaka
Akio
A
Hoshino
Takanobu
T
Murata
Nobuo
N
Hashimoto
Daijo
D
Itoyama
Shinji
S
Mori
Takashi
T
Matsumoto
Yoshiro
Y
Miura
Tsuyoshi
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014498:Uracil / Q000008:administration & dosage
D004338:Drug Combinations; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil