In vitro detection of cross-resistant and non-cross-resistant agents with fluorouracil for patients with colorectal cancer.
BACKGROUND
Fluorouracil-based chemotherapy, such as that with 5-fluorouracil (5-FU)/leucovorin, is standard as first-line chemotherapy for advanced colorectal cancer (CRC) in Japan. However, the best agent for second-line chemotherapy after fluorouracil failure is yet to be determined. This study was undertaken to find an appropriate agent for second-line chemotherapy.


METHODS
Seventy-five tumor specimens from CRC patients with no prior chemotherapy were obtained operatively and their chemosensitivity to five anticancer agents; i.e., 5-FU, mitomycin C (MMC), cisplatin, docetaxel, and an active metabolite of irinotecan (SN-38), was analyzed in an in vitro chemosensitivity test. In this method, the degree of chemosensitivity was expressed as the percent T/C ratio, where T was the total volume of the tumor colonies in the treated group and C was that of the control group. Pearson's correlation coefficients were used to assess the relationship between two agents.


RESULTS
Fifty-eight specimens (colon, 28; rectum, 30) were successfully analyzed. Positive correlations with 5-FU chemosensitivity were verified for the chemosensitivity of MMC, cisplatin, and docetaxel. No correlation with 5-FU chemosensitivity was verified for SN-38 chemosensitivity. Although the functional mechanism of each of the agents differs from that of 5-FU, with the exception of irinotecan, they all had a spectrum closely similar to the 5-FU spectrum.


CONCLUSIONS
Only irinotecan exhibited a spectrum independent of that of 5-FU, thus indicating that it could be an appropriate agent for second-line chemotherapy after fluorouracil failure.
Yamashita
Kazuki
K
Department of Surgery, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. kazuki@med.kawasaki-m.ac.jp
Urakami
Atsushi
A
Kubozoe
Tadahiko
T
Ikeda
Masaharu
M
Hirabayashi
Yoko
Y
Yamamura
Masahiro
M
Iki
Katsumichi
K
Akiyama
Takashi
T
Matsumoto
Hideo
H
Hirai
Toshihiro
T
Sadahira
Yoshito
Y
Tsunoda
Tsukasa
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D016685:Mitomycin; D000077146:Irinotecan; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin