title: Zilascorb(2H), a low-toxicity protein synthesis inhibitor that exhibits signs of anticancer activity in malignant melanoma.
abstract: Zilascorb(2H) is a benzaldehyde derivative giving rise to strong protein synthesis inhibition. It has shown antitumor activity against human malignant melanoma grown as xenografts in nude mice. The effect was manifest only after prolonged daily treatment and was quickly reversible when treatment was stopped. Drug-induced fever was the dose-limiting toxicity observed during clinical phase I studies of zilascorb(2H). The object of the present study was to assess antitumor activity, safety and tolerability of the drug in melanoma patients. Sixteen patients with disseminated malignant melanoma were included, all presenting with WHO performance status 0-2 and adequate organ functions. Previous chemo- or radiotherapy was accepted, while patients with known CNS metastases were excluded. Due to its low solubility and quickly reversible activity, zilascorb(2H) 1400 mg was infused by the patients twice daily through a venous access port for up to 12 weeks. Induction of tumor regression was demonstrated in one patient, who was, however, withdrawn from treatment after 2 weeks because of recurrent fever and fatigue. All the 12 patients evaluable for antitumor activity had progressive disease. Zilascorb(2H) was well tolerated, except for fever reactions and reversible liver toxicity. Most patients learned quickly how to handle a venous access port, but daily self-administration of i.v. infusions became too cumbersome to justify further patient inclusion despite the tumor regression observed. We conclude that zilascorb(2H) seems to have the potential for antitumor activity in metastatic malignant melanoma and is well tolerated. Daily self-administration of drug infusions is not desirable for long periods and zilascorb(2H) tablets have been developed. Because of its favorable toxicity profile, especially compared to other protein synthesis inhibitors, zilascorb(2H) may be particularly interesting for combinations with other anticancer drugs.
authors.affiliation: Department of Oncology, The Norwegian Radium Hospital, Oslo.
authors.forename: K A
authors.initials: KA
authors.lastname: Semb
authors.forename: S
authors.initials: S
authors.lastname: Aamdal
authors.forename: E
authors.initials: E
authors.lastname: Mette
authors.forename: C
authors.initials: C
authors.lastname: Ingvar
authors.forename: N
authors.initials: N
authors.lastname: Gullaksen
authors.forename: K
authors.initials: K
authors.lastname: Osmundsen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001597:Benzylidene Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D011500:Protein Synthesis Inhibitors; D001205:Ascorbic Acid; C070680:zilascorb