title: Phase I and pharmacokinetic study of DACA (XR5000): a novel inhibitor of topoisomerase I and II. CRC Phase I/II Committee.
abstract: DACA, also known as XR5000, is an acridine derivative active against both topoisomerase I and II. In this phase I study, DACA was given as a 3-h intravenous infusion on 3 successive days, repeated every 3 weeks. A total of 41 patients were treated at 11 dose levels between 9 mg m(-2) d(-1) and the maximum tolerated dose of 800 mg m(-2) day(-1). The commonest, and dose-limiting, toxicity was pain in the infusion arm. One patient given DACA through a central venous catheter experienced chest pain with transient electrocardiogram changes, but no evidence of myocardial infarction. At the highest dose levels, several patients also experienced flushing, pain and paraesthesia around the mouth, eyes and nose and a feeling of agitation. Other side-effects, such as nausea and vomiting, myelosuppression, stomatitis and alopecia, were uncommon. There was one minor response but no objective responses. DACA pharmacokinetics were linear and did not differ between days 1 and 3. The pattern of toxicity seen with DACA is unusual and appears related to the mode of delivery. It is possible that higher doses of DACA could be administered using a different schedule of administration.
authors.affiliation: CRC Department of Medical Oncology, Bearsden, Glasgow, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: C
authors.initials: C
authors.lastname: Gardner
authors.forename: A
authors.initials: A
authors.lastname: Flavin
authors.forename: J
authors.initials: J
authors.lastname: Sludden
authors.forename: I
authors.initials: I
authors.lastname: Dennis
authors.forename: J
authors.initials: J
authors.lastname: de Bono
authors.forename: P
authors.initials: P
authors.lastname: Beale
authors.forename: P
authors.initials: P
authors.lastname: Vasey
authors.forename: C
authors.initials: C
authors.lastname: Hutchison
authors.forename: M A
authors.initials: MA
authors.lastname: Macham
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.forename: N M
authors.initials: NM
authors.lastname: Bleehen
mesh_terms: D000166:Acridines / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010146:Pain; D018579:Patient Selection; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; C121181:DACA, acridine; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors