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

J Surg Oncol. 2000 Jan;73(1):6-11. doi: 10.1002/(sici)1096-9098(200001)73:1<6::aid-jso3>;2-q.


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 order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells.

Methods: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The 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 agents was measured to understand the mechanism of the augmentation.

Results: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic 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 for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect.

Conclusions: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Cisplatin / administration & dosage*
  • Colonic Neoplasms / drug therapy*
  • Coloring Agents
  • Drug Synergism
  • Female
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Rectal Neoplasms / drug therapy*
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Coloring Agents
  • Tetrazolium Salts
  • Thiazoles
  • Mitomycin
  • Irinotecan
  • thiazolyl blue
  • Cisplatin
  • Camptothecin