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

Gemcitabine (2',2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine , is an antineoplastic agent with clinical activity against several types o f cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor; is a drug with a broad spectrum of anticancer activity. Since these drugs have different m echanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performance on the MCF-7 breast cancel ann the SCO G small cell lung cancel (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobolo gram nm 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 conc entrations, combinations of gemcitabine and CPT-11 show a synergistic growt h inhibitory effect on MCF-7 cells, However, in SCOG cells CI analysis show ed synergy at concentrations of gemcitabine and CPT-11 greater than 1 mu M brit antagonism at combination concentrations less than 1 mu M. These precl inical cytotoxicity data provide an experimental basis for conducting clini cal trials using combinations of gemcitabine and CPT-11, especially in pati ents with breast and lung cancers.