Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines

Anticancer Res. Nov-Dec 1999;19(6B):5423-8.

Abstract

Gemcitabine (2'-2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine, is an antineoplastic agent with clinical activity against several types of cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor, is a drug with a broad spectrum of anticancer activity. Since these drugs have different mechanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performed on the MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobologram analysis revealed for the first time that the combination of these drugs exerted synergy over a wide range of concentrations in MCF-7 and SCOG cells. Moreover, combination index (CI) analysis revealed that at low concentrations, combinations of gemcitabine and CPT-11 show a synergistic growth inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis showed synergy at concentrations of gemcitabine and CPT-11 greater than 1 microM but antagonism at combination concentrations less than 1 microM. These preclinical cytotoxicity data provide an experimental basis for conducting clinical trials using combinations of gemcitabine and CPT-11, especially in patients with breast and lung cancers.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / pathology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Carcinoma, Small Cell / pathology*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Synergism
  • Humans
  • Irinotecan
  • Lung Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Irinotecan
  • gemcitabine
  • Camptothecin