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tumor regression was demonstrated in one patient, who was, however, withdrawn from treatment after 2 weeks because of recurrent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.