A phase IIA study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), administered at two different dose schedules in patients with platinum- and taxane-resistant/refractory ovarian cancer.

Abstract

OBJECTIVES:

There is an urgent need for new agents with activity in platinum- and taxane-resistant epithelial ovarian cancer. Exatecan mesylate is a novel topoisomerase I inhibitor with potent activity against ovarian cancer in vitro. A multicentre phase IIA study was conducted in patients with platinum- and taxane-resistant epithelial ovarian cancer.

PATIENTS AND METHODS:

Fifty-seven patients with bidimensionally measurable ovarian cancer, previously exposed to platinum and taxanes, whose disease had relapsed within 6 months of platinum-containing chemotherapy were randomised to one of two intravenous schedules of exatecan mesylate; 0.3 mg/m(2) daily for 5 days every 3 weeks (Arm A) or 2.1 mg/m(2) weekly for 3 weeks out of 4 (Arm B).

RESULTS:

There were no responses in the weekly arm and a radiological response rate of 5.3% (95% CI 0.3-21.8%) in the daily arm. Principal toxicities were myelosuppression and emesis. Grade 3/4 neutropenia occurred in 29% of patients in Arm A and 6% patients in Arm B. Seventy-one percent of patients in Arm A required red cell transfusions while on treatment.

CONCLUSIONS:

Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen.

• Authors: A Clamp, M Adams, R Atkinson, E Boven, A H Calvert, A Cervantes, T Ganesan, J Lotz, P Vasey, P Cheverton, G C Jayson
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 95 Issue 1 Pg. 114-9 (Oct 2004) ISSN: 0090-8258 [Print] United States
• PMID: 15385119 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents, Phytogenic
• Bridged-Ring Compounds
• Enzyme Inhibitors
• Organoplatinum Compounds
• Taxoids
• Topoisomerase I Inhibitors
• taxane
• exatecan
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Bridged-Ring Compounds (administration & dosage)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Drug Administration Schedule
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Enzyme Inhibitors (adverse effects, therapeutic use)
• Female
• Humans
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Ovarian Neoplasms (drug therapy)
• Taxoids (administration & dosage)
• Topoisomerase I Inhibitors