Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial.
BACKGROUND
The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival.


METHODS
A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat.


RESULTS
There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild.


CONCLUSIONS
A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.
Sadahiro
Sotaro
S
Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan. sadahiro@is.icc.u-tokai.ac.jp
Suzuki
Toshiyuki
T
Ishikawa
Kenji
K
Yasuda
Seiei
S
Tajima
Tomoo
T
Makuuchi
Hiroyasu
H
Saitoh
Takuro
T
Murayama
Chieko
C
D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016009:Chi-Square Distribution; D003082:Colectomy / Q000379:methods; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011322:Primary Prevention / Q000379:methods; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005472:Fluorouracil