Phenobarbital modifies antitumor effect of cyclophosphamide depending on the type of tumor cell death caused by it.

Antitumor effect of cyclophosphamide on LS and P388 tumors is realized via apoptosis and on HA-1 and Krebs-2 tumors resistant to apoptosis via necrosis of tumor cells. Phenobarbital induction of cyclophosphamide-metabolizing enzymes decreases and cimetidine inhibition potentiates the effect of cyclophosphamide on LS and P388 cells and does not modulate the effect on HA-1 and Krebs-2 cells. Presumably, apoptosis and necrosis of tumor cell are induced by different cyclophosphamide metabolites.