To determine the optimal combination of commonly used anticancer agents with 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4(1-piperidino)1-piperidino] carbonyloxy camptothecin (CPT-11), for chemotherapy of lung cancer, we studied the effects of SN-38 in combination with six representative anticancer agents on the human small cell lung cancer (SCLC) cell line, NCl N417, and the non-small cell lung cancer (NSCLC) cell line, PC-9. The anticancer activity was evaluated by MTT assay and the effects of drug combinations on ID50 were analyzed by an improved isobologram method. In the SCLC cell line, supra-additive effect was observed for SN-38 in combination with cisplatin, etoposide (VP-16) and paclitaxel (Taxol). An additive effect was observed for its combination with bleomycin. Sub-additive and protective effects were found in combination with adriamycin (ADR) and 5-fluorouracil (5-FU). In the NSCLC cell line, supra-additive and marginal supra-additive effects were found for SN-38 in combination with VP-16, ADR, 5-FU and bleomycin. The others showed additive effects with SN-38. No drug showed sub-additive and protective effects with SN-38. These results suggest that all the drugs we selected can be used with SN-38 simultaneously for NSCLC, while for SCLC, cisplatin, VP-16 and Taxol are the most suitable for combination with SN-38.
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