Effects of CPT-11 in combination with other anti-cancer agents in culture

Int J Cancer. 1992 Feb 20;50(4):604-10. doi: 10.1002/ijc.2910500420.


CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase-II evaluation. In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-11 and SN-38 (active substance of CPT-11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-11 or SN-38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-11 in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-11 in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-11.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • In Vitro Techniques
  • Irinotecan
  • Leukemia, Lymphoid / drug therapy*
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Camptothecin