Topotecan is a synthetic derivative of the naturally occurring compound camptothecin. Camptothecin belongs to a group of chemicals called alkaloids, and is extracted from plants such as Camptotheca acuminata. Captothecin was initially investigated as a chemotherapeutic agent due to its anti-cancer activity in laboratory studies. The chemical structure and biological action of topotecan is similar to that of camptothecin and irinotecan.
Topotecan inhibits the normal functioning of the enzyme topoisomerase I. The normal role of topoisomerase I is to aid in the replication, recombination and repair of deoxyribonucleic acid (DNA). Higher levels of
Topotecan is used in patients whose cancer of the ovary has recurred or progressed after platinum-based treatment such as cisplatin. Topotecan is also used to treat relapse of small cell lung cancer that initially responded to other drugs. Increases in survival times have been observed in patients treated with topotecan compared to control populations treated with paclitaxel.
Patients should be carefully monitored before and during topotecan treatment for bone marrow function.
Topotecan is administered intravenously over 30 minutes once per day for five consecutive days followed by 16 days of rest. This schedule may be repeated every 21 days. The initial dose of topotecan may be adjusted downward depending on patient tolerance to the toxic side effects of topotecan.
The dose of topotecan may be reduced in patients with kidney dysfunction.
No dose modification is necessary for patients with liver impairment.
No dose modification is necessary for elderly patients.
Topotecan should only be used under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Certain complications will only be possible to manage if the necessary diagnostic and treatment resources are readily available. Topotecan should not be used in patients with bone marrow depression before starting treatment. Skin that comes in contact with topotecan must be washed thoroughly with soap and warm water.
The dose of topotecan may be reduced in patients with moderate kidney dysfunction. Topotecan is not recommended for use in patients with severe kidney dys-function.
Topotecan should not be administered to pregnant women. Women of child bearing age are advised not to become pregnant during treatment. Women should discontinue nursing prior to taking topotecan.
Suppression of bone marrow function is the most serious side effect commonly observed in this treatment and can lead to death. Bone marrow reserves should be monitored by blood cell counts for all patients before and during topotecan treatment. The suppression of bone marrow is not cumulative over time. Additional side effects including nausea and vomiting, anorexia, diarrhea, constipation, headache and hair loss (alopecia) may occur.
Suppression of bone marrow is more severe when topotecan is given with platinum drugs. G-CSF (filgrastim) may extend the duration of bone marrow suppression. If G-CSF is used, it should not be administered until day six of the 21-day course.
See Also Lung cancer, small cell
—A nitrogen containing compound occuring in plants
—Loss of appetite and the inability to eat
—An active process in which a cell dies due ot a chemical signal. Programmed cell death.