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Indication: ovarian cancer
The treatment of advanced ovarian cancer includes platinum-based chemotherapy. Although many patients will respond to this chemotherapy, the disease recurs. Topotecan can now be offered to women with metastatic carcinoma of the ovary who have failed to respond to treatment.
Topotecan is an inhibitor of topoisomerase. This enzyme is involved in the replication of DNA and its concentrations are higher than normal in cancer cells. Topotecan destroys cancer cells, but also damages normal cells.
The drug is given as a 30-minute infusion every day for 5 days. After a 3-week break, the course is repeated and a minimum of 4 courses is recommended.
Topotecan has a high volume of distribution (up to 243 L after a single dose). The half-life of a dose is 2-7 hours with clearance mainly by metabolism, but 20-60% of the dose will appear in the urine. Plasma clearance is therefore reduced by both hepatic and renal impairment.
Paclitaxel is already available to treat women who have not responded to platinum-based chemotherapy, so this drug has been compared with topotecan. The median time to response for topotecan is approximately 10 weeks compared with 7 weeks for paclitaxel. However, the overall response rate maybe a little higher with topotecan than paclitaxel. For example, 6 of 112 patients given topotecan had a complete response compared with 4 of the 114 patients given paclitaxel. The median time for the disease to progress was longer inpatients given topotecan.
Unfortunately, topotecan is very toxic. The dose limiting toxicity is haematological with nearly all patients being affected. A neutropenia of <500 cells/mm3 occurs in 81% of patients. The neutropenia develops in 11 days and lasts for about a week. The full blood count should be monitored closely and patients who have had severe neutropenia should have their dose reduced or be given granulocyte-colony stimulating factor (G-CSF). Most patients will also develop anaemia and thrombocytopenia. Nearly 80% of the patients will have nausea and many will vomit. A majority of the women will develop alopecia.
Although some patients will respond to topotecan, the effect on survival is unclear.