title: Phase II study of XR 5000 (DACA), an inhibitor of topoisomerase I and II, administered as a 120-h infusion in patients with non-small cell lung cancer.
abstract: XR5000 is a tricyclic carboxamide-based cytotoxic agent that binds to DNA by intercalation and stimulates DNA cleavage by inhibition of both topoisomerase I and II. The aim of this study was to evaluate the antitumoral activity and safety profile of XR5000 given as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients received XR5000 at the dose of 3010 mg/m(2) as a 120-h central venous infusion every 3 weeks. The 15 patients (median age 56 years, range 48-71 years) enrolled had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (3 patients), 1 (11 patients) or 2 (1 patient). A total of 32 cycles of XR5000 (median 2, range 1-6) were given to 14 patients. No objective response (assessed according to World Health Organization (WHO) criteria) was documented in the 12 evaluable patients by an external review panel; in 4 out of the 12 patients disease stabilisation was recorded. The following toxicities graded according to the Common Toxicity Criteria (CTC) version 2.0. were observed: one grade 3 and two grade 4 granulocytopenia, one grade 3 and one grade 4 thrombocytopenia, one grade 3 deep venous thrombosis, one grade 3 fatigue, and grade 3 undocumented epileptic seizures which led to death in 2 patients. With only 4 out of 12 patients reaching stable disease when using this dose and regimen, further evaluation of XR5000 in advanced NSCLC is not justified.
authors.affiliation: Ludwig Boltzmann-Institute for Applied Cancer Research, (LBI-ACR VIEnna), Kaiser Franz Josef-Spital, 3rd Medical Department-Oncology, Kundratstrasse 3, 1100, Vienna, Austria. christian@kfj.magwein.gv.at
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
authors.forename: B
authors.initials: B
authors.lastname: Coudert
authors.forename: L
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.forename: M
authors.initials: M
authors.lastname: Salzberg
authors.forename: T
authors.initials: T
authors.lastname: Gamucci
authors.forename: X
authors.initials: X
authors.lastname: Paoletti
authors.forename: C
authors.initials: C
authors.lastname: Hermans
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000166:Acridines / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D020246:Venous Thrombosis / Q000139:chemically induced
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; C121181:DACA, acridine; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors