Phase I study of intravenous 4-hydroxyanisole.

Abstract

4-Hydroxyanisole is a depigmenting agent which has been shown to have activity against malignant melanoma when given intra-arterially in man. An intravenous dose escalation study has been carried out with the aim of obtaining maximum plasma concentrations in a 5 day schedule. 8 patients entered this study which was stopped because of drug toxicity after 3 patients had been treated at the third dose escalation of 15 g/m2. 2 patients had WHO grade 4 liver and one also grade 4 renal toxicity and another had grade 4 haemoglobin toxicity. Extrapolated plateau plasma levels between 112 and 860 mumol/l were obtained, which in vitro studies suggested would be cytotoxic. Hopefully, newer analogues will have a greater specificity for the melanin pathway with less toxicity.

• Authors: G J Rustin, M R Stratford, A Lamont, N Bleehen, P A Philip, N Howells, R R Watfa, J A Slack
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 28A Issue 8-9 Pg. 1362-4 ( 1992) ISSN: 0959-8049 [Print] England
• PMID: 1515252 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anisoles
• Antineoplastic Agents
• mequinol

Topics

• Anisoles (pharmacokinetics, therapeutic use)
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Drug Administration Schedule
• Drug Evaluation
• Evaluation Studies as Topic
• Humans
• Infusions, Intravenous
• Lymphatic Metastasis
• Melanoma (blood, drug therapy)
• Pigmentation (drug effects)
• Skin Neoplasms (blood, drug therapy)