Hepatic recurrence after prophylactic hepatic arterial infusion of 5-fluorouracil for Dukes' C colorectal cancer--correlation with the expression of dihydropyrimidine dehydrogenase in the primary tumor

• Published in: Gan to kagaku ryoho Vol. 29; no. 12; p. 2267
• Main Authors: Ishida, Hideyuki, Takeuchi, Ikuya, Ohsawa, Tomonori, Nakada, Hiroshi, Ishizuka, Naoki, Yokoyama, Masaru, Inokuma, Shigehisa, Suzuki, Tsuyoshi, Yamada, Hirofumi, Odaka, Akio, Hoshino, Takanobu, Murata, Nobuo, Hashimoto, Daijo, Matsumoto, Yoshiro, Miura, Takeshi
• Format: Journal Article
• Language: Japanese
• Published: Japan 01-11-2002
• Subjects: Administration, Oral; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Colonic Neoplasms - pathology; Colonic Neoplasms - surgery; Dihydrouracil Dehydrogenase (NADP); Enzyme-Linked Immunosorbent Assay; Fluorouracil - administration & dosage; Humans; Infusions, Intra-Arterial; Liver Neoplasms - prevention & control; Liver Neoplasms - secondary; Neoplasm Recurrence, Local; Oxidoreductases - analysis; Tegafur - administration & dosage; Uracil - administration & dosage
• ISSN: 0385-0684

The purpose of this study was twofold: (1) to disclose the intermediate outcome of a non-randomized trial of prophylactic hepatic arterial infusion chemotherapy (PHAI) for curatively resected Dukes' C colorectal cancer performed between November 1996 and April 2000, and (2) to examine the relationship between the expression of dihydropyrimidine dehydrogenase (DPD) in tumor tissue and the efficacy of this chemotherapy.
The oncological outcomes were compared between patients (n = 28) receiving PHAI (5-FU: 500 mg/body/w x 50 cycles) plus oral administration of UFT-E (400 mg/body/day, for 24 months) and those (n = 21) receiving UFT-E alone. The levels of tumoral DPD were determined in a total of 43 patients (n = 25, PHAI group; n = 18, control group) by an enzyme-linked immunosorbent assay.
Seven (25%) in the PHAI group and four (19%) in the control group developed liver metastasis postoperatively. The liver metastasis-free survival was not different between the groups (p = 0.94). When the analysis was restricted to patients who developed liver metastasis, the duration from surgery to detecting liver metastasis tended to be longer in the PHAI group (p = 0.09). In addition, the overall survival tended to be better in the PHAI group (p = 0.12). In the control group, the level of DPD was higher in patients who developed liver metastases (n = 4) than in those who did not (n = 14, p = 0.04). However, in the PHAI group, the level of DPD was not different regardless of the occurrence of liver metastases (p = 0.30).
These results suggest that (1) PHAI is unlikely to improve the prognosis of Dukes' C patients remarkably, and (2) the efficacy of this regimen cannot be predicted by determining the levels of tumoral DPD.