In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer

Background and Objectives: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In orde r to promote the clinical response of chemotherapy for colorectal cancer us ing CPT-11, one of the most effective strategies is to use it in combinatio n with other anticancer agents. In the present study, anticancer effects af ter combining CPT-II and other antitumor agents were determined by a 3-(4,5 -di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of col orectal cancer cells, especially freshly isolated cancer cells. Methods: Freshly isolated cancer cells from 20 patients with colorectal can cer and the established colon cancer cell lines were used in this study. Th e augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy CPT (SN -38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agent s was measured to understand the mechanism of the augmentation. Results: The percent inhibition of SN-38 in combination with cisplatin (CDD P) and mitomycin revealed a high anticancer effect compared with each antic ancer agent alone for freshly isolated rectal cancer. CDDP also had a syner gistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP fo r freshly isolated colorectal cancer. This augmentation showed a strong syn ergistic effect. Conclusions: These results: may be supportive to ongoing clinical studies o f chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer. J. Surg. Oncol. 2000;73:6-11. (C) 2000 Wiley-Liss, Inc.