Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.
OBJECTIVE
Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen.


METHODS
Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive.


RESULTS
One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9).


CONCLUSIONS
Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.
Creemers
G J
GJ
Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), The Netherlands.
Bolis
G
G
Gore
M
M
Scarfone
G
G
Lacave
A J
AJ
Guastalla
J P
JP
Despax
R
R
Favalli
G
G
Kreinberg
R
R
Van Belle
S
S
Hudson
I
I
Verweij
J
J
Ten Bokkel Huinink
W W
WW
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan
D000970:Antineoplastic Agents; D019772:Topotecan; D002945:Cisplatin; D002166:Camptothecin