ZILASCORB(H-2), A LOW-TOXICITY PROTEIN-SYNTHESIS INHIBITOR THAT EXHIBITS SIGNS OF ANTICANCER ACTIVITY IN MALIGNANT-MELANOMA

Zilascorb(H-2) is a benzaldehyde derivative giving rise to strong prot ein synthesis inhibition. It has shown antitumor activity against huma n malignant melanoma grown as xenografts in nude mice. The effect was manifest only after prolonged daily treatment and was quickly reversib le when treatment was stopped. Drug-induced fever was the dose-limitin g toxicity observed during clinical phase I studies of zilascorb(H-2). The object of the present study was to assess antitumor activity, saf ety and tolerability of the drug in melanoma patients. Sixteen patient s with disseminated malignant melanoma were included, all presenting w ith WHO performance status 0-2 and adequate organ functions. Previous chemo- or radiotherapy was accepted, while patients with known CNS met astases were excluded. Due to its low solubility and quickly reversibl e activity, zilascorb(H-2) 1400 mg was infused by the patients twice d aily through a venous access port for up to 12 weeks. Induction of tum or regression was demonstrated in one patient, who was, however, withd rawn from treatment after 2 weeks because of recurrent fever and fatig ue. All the 12 patients evaluable for antitumor activity had progressi ve disease. Zilascorb(H-2) was well tolerated, except for fever reacti ons and reversible liver toxicity. Most patients learned quickly how t o handle a venous access port, but daily self-administration of i.v. i nfusions became too cumbersome to justify further patient inclusion de spite the tumor regression observed. We conclude that zilascorb(H-2) s eems to have the potential for antitumor activity in metastatic malign ant melanoma and is well tolerated. Daily self-administration of drug infusions is not desirable for long periods and zilascorb(H-2) tablets have been developed. Because of its favorable toxicity profile, espec ially compared to other protein synthesis inhibitors, zilascorb(H-2) m ay be particularly interesting for combinations with other anticancer drugs. [(C) 1998 Lippincott Williams & Wilkins.].