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Lookup NU author(s): Professor Alan Calvert
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Trimelamol is an analogue of hexamethylmelamine and pentamethylmelamine which does not require metabolic activation and is sufficiently soluble to allow parenteral administration. A Phase I trial has been performed at the Royal Marsden Hospital in which two schedules of administration have been evaluated, a single i.v. infusion repeated every 3 weeks and 3 daily doses repeated every 3 weeks. Pharmacokinetic analysis was performed at all dose levels on both schedules and a linear correlation was demonstrated between dose and area under the curve. Myelosuppression was dose limiting for single dose administration with a maximum tolerated dose of 2400 mg/m2. Median leukocyte nadirs at 1800, 2100, and 2400 mg/m2 were 3.2, 2.6, and 1.5 x 109/liter. Thrombocytopenia and anemia also occurred but were not dose limiting. Doses >1500 mg/m2 caused WHO grade 3 nausea and vomiting but no acute sedation. Three day administration appeared to be less myelosuppressive, giving a maximum tolerated dose of 1000 mg/m2. Median leukocyte nadirs at 800, 900, and 1000 mg/m2 daily for 3 days were 3.0, 2.3, and 1.5 x 109/liter. Nonhematological toxicities were also less marked on the fractionated schedule. Antitumor effects were observed including 1 complete and 9 partial responses. Demonstration of activity in ovarian cancer has led to further evaluation in this disease using the 3-day schedule at a dose of 800 mg/m2 daily for 3 days.
Author(s): Judson IR, Calvert AH, Rutty CJ, Abel G, Gumbrell LA, Graham MA, Evans BD, Wilman DEV, Ashley SE, Cairnduff F
Publication type: Article
Publication status: Published
Journal: Cancer Research
Year: 1989
Volume: 49
Issue: 19
Pages: 5475-5479
Print publication date: 01/10/1989
ISSN (print): 0008-5472
ISSN (electronic): 1538-7445
URL: http://cancerres.aacrjournals.org/cgi/content/abstract/49/19/5475
PubMed id: 267020
