Phase I study of intravenous 4-hydroxyanisole.
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.
Rustin
G J
GJ
Cancer Treatment Centre, Mount Vernon Hospital, Northwood, Middlesex, U.K.
Stratford
M R
MR
Lamont
A
A
Bleehen
N
N
Philip
P A
PA
Howells
N
N
Watfa
R R
RR
Slack
J A
JA
D000840:Anisoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005069:Evaluation Studies as Topic; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D010858:Pigmentation / Q000187:drug effects*; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy*
D000840:Anisoles; D000970:Antineoplastic Agents; C009760:mequinol