New chemotherapeutics in malignant mesothelioma: effects on cell growth and IL-6 production

Purpose: The benefits of chemotherapy can be assessed in terms of tumour sh rinkage, prolongation of Life or simply palliation of symptoms. In the stud y reported here, in vitro correlates of these parameters were sought as a r ational guide to the choice of newer agents in the clinic. Methods: The cyt otoxicity and effects on IL-6 production of ten chemotherapy agents represe nting four different classes of drugs were tested against a panel of five m esothelioma cell lines. Results: The mesothelioma cells were more sensitive to the action of irinotecan (and its active metabolite SN38) and gemcitabi ne than the control cell lines. Gemcitabine and to a lesser extent irinotec an inhibited the secretion of the proinflammatory cytokine IL-6 at concentr ations of each drug that produced only small decreases in cell viability. T his effect was not seen in cells treated with docetaxel or vindesine. Highe r doses of gemcitabine and irinotecan caused a surge in IL-6 release and th is was not due to release of intracellular stores of IL-6 through lysis of the cells. Conclusions: These results suggest that irinotecan and gemcitabi ne are not only more likely to be active against mesothelioma than other ne w chemotherapy agents but may also produce a palliative effect in nonrespon ders to these agents by decreasing the secretion of IL-6.