Mithramycin therapy in advanced testicular neoplasms

Mithramycin is an antibiotic that produces inhibition of the synthesis of RNA in vivo and in vitro. Antitumor activity against germinal neoplasms of the testis has been associated with severe toxicity and a high mortality rate. The study of the synthesis of RNA in an experimental mouse glioma and in mouse liver following treatment with mithramycin revealed a marked dissociation between the rate of recovery of these 2 tissues from the RNA inhibitory effect. Whereas liver rapidly recovered its capacity for RNA synthesis, the recovery of the tumor was delayed. This suggested that an alternate-day dosage schedule might reduce toxicity while maintaining an antitumor effect in 23 patients with advanced testicular neoplasms treated with an alternate-day dosage regimen, there was no drug-induced mortality, drug toxicity was markedly reduced, and antitumor effect was maintained. Therapeutic index of mithramycin has been greatly improved by rational selection of a dosage schedule.