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Semb KA; Aamdal, S; Mette, E; Ingvar, C; Gullaksen, N; Osmundsen, K
Anti-Cancer Drugs: October 1998
Research Papers: PDF Only

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 dally treatment and was quickly reversible when treatment was stopped. Drug-induced fever was the doselimiting toxicity observed during clinical phase I studies of zilascorb(2H). The object of the present study was to assess antitumor activity, safety and tolerablllty 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, zllascorb(2H) 1400 mg was infused by the patients twice dally 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 Induction of tumor regression was demonstrated In one patient, who was, however, withdrawn from treatment after 2 weeks because of recurrent fever and fatigue.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. Zllascorb(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 selfadministration 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-admlnistratlon 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. [© 1998 Lippincott Williams & Wilkins.]

© 1998 Lippincott Williams & Wilkins, Inc.