EFFECT OF CPT-11 IN COMBINATION WITH OTHER ANTICANCER AGENTS IN LUNG-CANCER CELLS

To determine the optimal combination of commonly used anticancer agent s with 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite o f 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 hu man small cell lung cancer (SCLC) cell line, NCI N417, and the non-sma ll cell lung cancer (NSCLC) cell line, PC-9. The anticancer activity w as evaluated by MTT assay and the effects of drug combinations on ID50 were analyzed by an improved isobologram method. In the SCLC cell lin e, supra-additive effect was observed for SN-38 in combination with ci splatin, etoposide (VP-16) and paclitaxel (Taxol). An additive effect was observed for its combination with bleomycin, Sub-additive and prot ective effects were found in combination with adriamycin (ADR) and 5-f luorouracil (5-FU). In the NSCLC cell line, supra-additive and margina l supra-additive effects were found for SN-38 in combination with VP-1 6, ADR, 5-FU and bleomycin. The others showed additive effects with SN -38. No drug showed sub-additive and protective effects with SN-38. Th ese results suggest that all the drugs we selected can be used with SN -38 simultaneously for NSCLC, while for SCLC, cisplatin, VP-16 and Tax ol are the most suitable for combination with SN-38.