Hr. Bahadori et al., Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines, ANTICANC R, 19(6B), 1999, pp. 5423-5428
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.