Repeated hepatic intra-arterial chemotherapy based on results of anticancer drug sensitivity test in patients with synchronous hepatic metastases from colorectal cancer.
OBJECTIVE
We determined whether hepatic intra-arterial infusion of 5-fluorouracil (5-FU) in patients with synchronous hepatic metastases from colorectal cancer, in whom the primary lesion was resectable but hepatic metastatic lesions were non-resectable helped improve survival time when administered on the basis of the results of the anticancer drug sensitivity test.


METHODS
The study population consisted of 29 patients with synchronous hepatic metastases from colorectal cancer who underwent surgical resection of the primary lesion alone. Of these 29 patients, 21 received hepatic intra-arterial infusion of 5-FU postoperatively after the 5-FU sensitivity test. The remaining 8 patients underwent surgical resection of the primary lesion but neither sensitivity testing nor hepatic intra-arterial chemotherapy. Tissue fragments were cultured, with each concentration of 5-FU in the thermoreversible gelation polymer forming a three-dimensional structure at 37 degrees C. The viability of tumor cells was evaluated according to WST methods; inhibitory concentration of 50% (IC50) values were calculated. We considered cancer tissue to be sensitive to IC50 values that were below twice the peak plasma concentration (120 microg/ml).


RESULTS
Of the 21 patients, 10 had sensitivity to 5-FU and 11 had no sensitivity. The response rates were 90.0% and 9.1%, respectively. The median survival times were 38 months and 10 months in these groups, respectively, and 7 months in patients who received no chemotherapy. This finding indicates a significantly longer survival time in the sensitive group, compared with either the insensitive group or the no chemotherapy group (P = .0014 P = .0023). The cumulative survival rate was significantly higher in the sensitive group compared with the insensitive group (P = .0001)


CONCLUSIONS
Ultimately, the group with sensitivity to 5-FU showed a significantly longer median survival time than the insensitive group.
Matsuoka
Hiromitsu
H
Department of General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.
Nagaya
Masaki
M
Tsukikawa
Satoshi
S
Yanagi
Yoshihiro
Y
Isogai
Akiko
A
Kubota
Sunao
S
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D046509:Tissue Culture Techniques
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil