Anticonvulsant drugs fail to modulate chemotherapy-induced cytotoxicity and growth inhibition of human malignant glioma cells

Adjuvant chemotherapy after cytoreductive surgery and irradiation plays an increasingly important role in the management of human malignant glioma. Here we have examined the effect of three anticonvulsants most commonly administered to glioma patients, carbamazepine, phenytoin and valproic acid, on the cytotoxic and antiproliferative actions in vitro of several cancer chemotherapy drugs currently evaluated for human gliomas. We find that none of the anticonvulsants reduces glioma cell viability or proliferation or modulates glioma cell clonogenicity at clinically relevant concentrations when administered alone. Therapeutic concentrations of either drug fail to alter the effect of cancer chemotherapy drugs in acute cytotoxicity assays or modified clonogenicity assays. A lack of interactions of anticonvulsants and cytotoxic drugs is also observed when the glioma cells are preexposed to the anticonvulsants for prolonged times, suggesting that chronic exposure to anticonvulsants in vivo may not change intrinsic glioma cell sensitivity to cancer chemotherapy. Thus, changes in hepatic enzyme activity or immunological parameters, but not modulation of intrinsic chemotherapeutic drug sensitivity, may influence the choice of an anticonvulsant for seizure control in glioma patients receiving adjuvant chemotherapy.