Phase 2 evaluation of topotecan administered on a 3-day schedule in the treatment of platinum- and paclitaxel-refractory ovarian cancer.
PURPOSE; The aim of this study was to investigate the toxicity and efficacy of a more convenient topotecan administration schedule (in contrast to the "standard" 1.5 mg/m(2)/day x 5 days q 21 days) in the management of platinum- and paclitaxel-refractory ovarian cancer.


METHODS
Patients with clinically defined platinum- and paclitaxel-refractory ovarian cancer participating in this phase 2 trial conducted by the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center received topotecan at a dose of 1.5 mg/m(2)/day x 3 days on a 21-day schedule. Both dose escalations and reductions were permitted in the protocol design.


RESULTS
A total of 29 patients (median age: 61; range: 43-80) were treated with this modified topotecan schedule. These individuals had received a median of two prior regimens (range: 1-4) (retreatment with a platinum agent or paclitaxel considered a single regimen). The median number of topotecan courses delivered was 3 (range: 1-7). Major toxicity included grade 4 neutropenia (24% of patients); neutropenic fever (10%); grade 3 thrombocytopenia (10%); and requirement for blood transfusion (14%). Dose escalation was possible, and dose reductions required, in 14 and 28% of patients, respectively. Two patients exhibited evidence of a clinically relevant response to treatment.


CONCLUSIONS
This 3-day topotecan program is more convenient and less toxic than the standard 5-day regimen. The limited level of activity observed is not inconsistent with that previously reported for the 5-day topotecan infusion schedule in platinum/paclitaxel-refractory ovarian cancer. Further investigation will be required to document the clinical utility of a 3-day topotecan schedule in a less heavily pretreated and more chemosensitive patient population.
Markman
M
M
Gynecologic Cancer Program, The Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA.
Kennedy
A
A
Webster
K
K
Kulp
B
B
Peterson
G
G
Belinson
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000378:metabolism; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017239:Paclitaxel / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D018394:CA-125 Antigen; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin