Topotecan
Indications
Topotecan is used for:
For the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage iv-b, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy
Adult Dose
Child Dose
Renal Dose
Administration
Contra Indications
Precautions
Pregnancy-Lactation
Interactions
Adverse Effects
Side effects of Topotecan :
Mechanism of Action
Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the s-phase of dna synthesis. Topoisomerase i relieves torsional strain in dna by inducing reversible single strand breaks. Topotecan binds to the topoisomerase i-dna complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in dna. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a dna base pair and binds at the site of dna cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream dna, thus preventing religation of the cleaved strand. By specifically binding to the enzyme>substrate complex, topotecan acts as an uncompetitive inhibitor