Phase i study of 2-amino-5-bromo-6-phenyl-4(3h)-pyrimidinone (ABPP), an oral interferon inducer, in cancer patients

A. Rios, D. A. Stringfellow, F. A. Fitzpatrick, S. B. Reele, G. D. Gutknecht, E. M. Hersh

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

2-Amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) was given to 59 patients in a Phase I study. The agent was selected because it is an interferon inducer and an immunotherapeutic agent in animal tumor models. The study was conducted in two phases. In the first phase, the drug was administered as a single oral dose of 25–2,000 mg/m2. In the second part, the highest tolerated dose reached during part one was used as the initial dose in a multiple-dose scheme of treatment. Patients were treated weekly. The dose was escalated each week, starting with a dose of 2 g/m2 and escalating to 3, 4, and 5 g/m2. No cardiac, hematologic, hepatic, or renal toxicity was observed. The most common toxicity was nausea and vomiting, which occurred in 18% of the patients; others were headache (8%). abdominal pain (8%), and diarrhea (6%). No consistent induction of interferon and no major modification of host defense parameters occurred. One patient with malignant melanoma showed evidence of tumor regression. Pharmacologic studies demonstrated a significant decrease in the bioavailability of the drug as it was administered in this study. Further studies of ABPP with a preparation that has good availability are indicated to determine the potential antitumor activity of this agent or this class of agents in humans.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalJournal of Biological Response Modifiers
Volume5
Issue number4
StatePublished - Aug 1986

Keywords

  • Immunomodulator
  • Immunotherapeutic
  • Inducer
  • Interferon
  • Phase I
  • Pyrimidinone

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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