title: Phase II study of XR 5000, an inhibitor of topoisomerases I and II, in advanced colorectal cancer.
abstract: XR 5000 is one of a series of tricyclic carboxamide-based cytotoxic agents. It binds to DNA by intercalation and stimulates DNA cleavage by inhibition of both topoisomerase I and II, thus possibly overcoming the resistance resulting from downregulation of either enzyme. Twenty patients with advanced or metastatic colorectal cancer, unpretreated for metastatic disease, received XR 5000 at the dose of 3010 mg/m(2) in a 120-h central intravenous (i.v.) infusion every 3 weeks. Response was evaluated every two cycles. No complete (CR) or partial responses (PR) were observed in eligible patients (response rate, 0 of 19, 0%; 95% confidence interval (CI): 0-18%). 5 patients had stable disease, which lasted from 79 to 157 days. Haematological toxicity was low, since only one grade 4 neutropenia and two grade 3 anaemia were observed. Other treatment-related grade 3-4 toxicities were: deep venous thrombosis (2 cases), liver toxicity, diarrhoea, anorexia, dyspnoea, chest pain, infection (1 case each). Despite the good toxicity profile, these results do not support further trials with XR 5000 in metastatic colorectal cancer.
authors.affiliation: EORTC Early Clinical Studies Group, New Drug Development Program, Brussels, Belgium. fracap@sirio-oncology.it
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
authors.forename: J B
authors.initials: JB
authors.lastname: Sorensen
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: F
authors.initials: F
authors.lastname: Duffaud
authors.forename: L
authors.initials: L
authors.lastname: Paz Ares
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: C
authors.initials: C
authors.lastname: de Balincourt
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000166:Acridines / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; C121181:DACA, acridine; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors