Inosiplex for Localized Herpes Zoster in Childhood Cancer Patients: Preliminary Controlled Study

Abstract

By multiple criteria, inosiplex-a reputed stimulator of virus-sensitized lymphocytes-had no demonstrable therapeutic effects in a preliminary controlled study of patients with localized herpes zoster and cancer. Lymphocytes from the six drug-treated patients were no more responsive to varicella-zoster antigen and phytohemagglutinin than were lymphocytes from seven patients who received a placebo.Inosiplex (p-acetamidobenozoic acid salt of inosine-dimethylaminoisopropanol acid in a 1:3 molar ratio) is presently under investigation as an antiviral agent with broad-spectrum effects. Based on results obtained with in vitro systems (12), laboratory animals (9, 11), and human volunteers (4), the drug's mechanism of action appears to involve a stimulation of the cellular immune system, in particular the "activated lymphocytes" that have been previously sensitized to foreign viral protein. Evidence that impaired cellular immunity can prevent or delay recovery from viral infections has come from studies by Blanden in an animal model (1-3) and in patients with congenital abnormalities of the immune system (6, 10).Herpes zoster infection provides an excellent model for evaluating the therapeutic efficacy of inosiplex. patients with zoster have had a previous exposure to varicella-zoster virus (VZV) because of earlier episodes ofvaricella and therefore should have a population of sensitized lymphocytes. Moreover, the extent of zoster infection can be readily determined from counts of cutaneous lesions. In the present study, inosiplex treatment was evaluated on the basis of four principal determinants: (i) progression of lesions within the dermatome after the beginiing of drug therapy, (ii) maximum percentage of dermatome involvement, (iii) skin dissemination and the associated viremia, (iv) responsiveness of lymphocytes to VZV antigen and phytohemagglutinin (PHA) in vitro.Contingent on informed written consent, 13 children with cancer and herpes zoster were randomly selected by a double-blind technique to receive either oral inosiplex (six patients) or a placebo with an identical appearance and taste (seven patients). To be enrolled in the study,

Chemotherapy of Viral Infections

“…FELDMAN et al (1978) found that children with neoplasms who developed herpes zoster infection did not show improvement with inosiplex. Again reports have been both negative and positive.…”