Efficacy and tolerability of lower-dose topotecan in recurrent ovarian cancer: a retrospective case review

Abstract

Topotecan (1.5 mg/m(2)/day for 5 consecutive days of a 21-day cycle) is an established recurrent ovarian cancer treatment, but myelosuppression can be dose limiting. This study evaluates the activity and tolerability of low-dose topotecan in our clinical experience. Case records were reviewed for patients with recurrent ovarian cancer in first through third relapse. Eligible patients had received > or =2 cycles of < or =1.25 mg/m(2) topotecan. Adverse events were evaluated using laboratory and clinical evaluation data. Twenty-seven eligible patients, most with advanced disease, received a total of 209 cycles (median, six cycles). Grade 3 or 4 hematologic toxicities during 184 cycles in 24 assessed patients were neutropenia, leukopenia, thrombocytopenia, and anemia in 35%, 28%, 36%, and 11% of cycles, and 21, 19, 16, and 10 patients, respectively. Only four grade 4 toxicities occurred: anemia (one) and thrombocytopenia (three). Myelosuppression was reversible, noncumulative, and manageable. Moreover, nonhematologic toxicity was generally mild to moderate, and the only two grade 3 events were constipation and deep vein thrombosis. Low-dose topotecan was active in this setting. Lower-dose topotecan is generally well tolerated and active in patients with pretreated ovarian cancer. Prospective clinical trials of low-dose topotecan in recurrent ovarian cancer are warranted.

Defective Mre11-dependent Activation of Chk2 by Ataxia Telangiectasia Mutated in Colorectal Carcinoma Cells in Response to Replication-dependent DNA Double Strand Breaks

“…Clinical investigations could also benefit from an understanding of the underlying genetic background that determines the activity of topotecan in ovarian cancers (75,76).…”

Systemische Therapie der epithelialen serösen Ovarialkarzinome

“…Die schwerwiegende Toxizität ist überwiegend hämatologischer Natur. Mehrere Studien haben niedrigere Anfangsdosen (d. h. 1 bis 1,25 mg/m 2 für 5 Tage alle 21 Tage) vorgeschlagen, um die hämatologische Toxizität zu verbessern 59 60 .…”

New, Expanded, and Modified Use of Approved Antineoplastic Agents in Ovarian Cancer

“…Several noncomparative phase II trials and retrospective reviews of institutional experience in recurrent and resistant ovarian cancer have shown that it is possible to achieve reasonable objective response rates by employing a lower dose (1.0 or 1.25 mg/m 2 ) during a 5-day treatment program [21][22][23], administering the drug on a 3-day regimen [24,25] or delivering the agent on a weekly schedule [26 -28]. In addition, these modified strategies result in a substantial reduction in the toxicities associated with use of topotecan in this palliative clinical setting.…”