In vitro, the combination resulted in a marked potentiation of temozolomide toxicity in Ewing sarcoma (50-fold) and ALL (30-fold) cell lines.In vivo, toxicity was comparable for both combinations. Both exhibited significant antitumor effects and induced total tumor regression in 5 of 10 Ewing xenografts, within 6 weeks of treatment. It was successful against xenografts with low MGMT expression (i.e., GBM2 glioblastoma and Rh28 rhabdomyosarcoma) and those with defective homologous recombination (i.e., KT-10 Wilms tumor). The gene discussed is MGMT; the disease is rhabdomyosarcoma.