Phase I and pharmacokinetic study of DACA (XR5000): a novel inhibitor of topoisomerase I and II

DACA, also known as XR5000, is an acridine derivative active against both t opoisomerase I and II. In this phase I study, DACA was given as a 3-h intra venous infusion on 3 successive days, repeated every 3 weeks. A total of 41 patients were treated at II dose levels between 9 mg m(-2) d(-1) and the m aximum tolerated dose of 800 mg m(-2) day(-1). The commonest, and dose-limi ting, toxicity was pain in the infusion arm. One patient given DACA through a central venous catheter experienced chest pain with transient electrocar diogram changes, but no evidence of myocardial infarction. At the highest d ose levels, several patients also experienced flushing, pain and paraesthes ia around the mouth, eyes and nose and a feeling of agitation. Other side-e ffects, such as nausea and vomiting, myelosuppression, stomatitis and alope cia, 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 adm inistered using a different schedule of administration.