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.
OBJECTIVE
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.


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.
Clamp
A
A
Cancer Research UK Deparment of Medical Oncology, Christie Hospital, M20 4BX, UK.
Adams
M
M
Atkinson
R
R
Boven
E
E
Calvert
A H
AH
Cervantes
A
A
Ganesan
T
T
Lotz
J
J
Vasey
P
P
Cheverton
P
P
Jayson
G C
GC
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; C080625:taxane; C095887:exatecan; D002166:Camptothecin