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 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.
Bahadori
H R
HR
Department of Experimental Oncology, Medical University of South Carolina, Charleston 29425, USA.
Rocha Lima
C M
CM
Green
M R
MR
Safa
A R
AR
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine