Phase II study of XR5000 (DACA), an inhibitor of topoisomerase I and II, administered as a 120-h infusion in patients with advanced ovarian cancer.
BACKGROUND
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 the present study was to evaluate the antitumoral activity and safety profile of XR5000 given as second-line chemotherapy in patients with ovarian cancer who had relapsed within 1 year after first-line chemotherapy with taxanes and platinum for advanced disease.


METHODS
Patients received XR5000 at the dose of 3010 mg/m(2) through a 120-h central venous infusion every 3 weeks. Toxicity was graded according to the Common Toxicity Criteria (CTC), version 2.0. An independent panel assessed response every two cycles according to the World Health Organization (WHO) criteria. Gehan's rule was used for sample size determination.


RESULTS
Sixteen patients were enrolled; one patient was ineligible because of prior melphalan single agent treatment. Eastern Cooperative Oncology Group (ECOG) performance status was 0 (eight patients), 1 (five patients), or 2 (two patients). The 15 eligible patients received 43 cycles of XR5000 (median 2, range 1-8). Hematological toxicity was mild with only one grade 3 anemia in one patient. Other drug-related toxicities never exceeded grade 3 and included fatigue (four patients), thrombosis (one patient), nausea (one patient), stomatitis (one patient) as well as dyspnea/cough (one patient). One patient who had refused further therapy and controls after the first cycle was not assessable for response evaluation. No objective responses were observed. Four patients experienced stable disease and 10 patients progressive disease. The median time to progression was 42 days (CI 95% 40; 54).


CONCLUSIONS
The complete lack of any objective response does not justify further evaluation of XR5000 in patients with advanced ovarian cancer using this dose and schedule, although the therapy was generally well tolerated.
Ludwig Boltzmann-Institute for Applied Cancer Research (LBI-ACR VIEnna), Kaiser Franz Josef-Spital, Vienna, Austria. christian.dittrich@wienkav.at
Christian
C
Dittrich
Veronique
V
Dieras
Pierre
P
Kerbrat
Cornelis
C
Punt
Roberto
R
Sorio
Francesco
F
Caponigro
Xavier
X
Paoletti
Christine
C
de Balincourt
Denis
D
Lacombe
Pierre
P
Fumoleau
D000166:Acridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome
D000166:Acridines; D000970:Antineoplastic Agents; C121181:DACA, acridine; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors