Key Terms: Alkaloid, Anorexia.
Definition
Topotecan is a drug used to treat certain types of cancer. Topotecan is available under the trade name Hycamtin, and may also be referred to as topotecan hydrochloride or topotecan HCl.
Purpose
Topotecan is an antineoplastic agent used to treat small cell lung cancer, and certain cancers of the ovary.
As of late 2003, clinical trials are underway in Italy and France to test the effectiveness of topotecan in treating tumors of the brain (glioblastomas) and autonomic nervous system (neuroblastomas). In the French study, topotecan is given together with radiotherapy while the Italian trial uses topotecan as part of combination chemotherapy. Early results indicate that the drug may be useful in treating cancers of the nervous system as well as ovarian and small-cell lung cancers.
Description
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 topoisomerase I have been found in certain cancer tumors compared to healthy tissue. Inhibiting topoisomerase I causes DNA damage. This damage leads to apoptosis, or programmed cell death.
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.
Tumors that are targeted by topotecan sometimes develop resistance to the drug. Although the reasons for this resistance are not fully understood as of late 2003, researchers think that they may be related either to inadequate amounts of drug in the tumor or to alterations in topoisomerase I that make the enzyme resistant to topotecan.
Recommended Dosage
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.
Precautions
Topotecan should be used only 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 dysfunction.
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.
Side Effects
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.
Interactions
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.
Resources
Periodicals
Garaventa, A., R. Luksch, S. Biasotti, et al. "A Phase II Study of Topotecan with Vincristine and Doxorubicin in Children with Recurrent/Refractory Neuroblastoma." Cancer 98 (December 1, 2003): 2488–2494.
Lesimple, T., M. B. Hassel, D. Gedouin, et al. "Phase I Study of Topotecan in Combination with Concurrent Radiotherapy in Adults with Glioblastoma." Journal of Neurooncology 65 (November 2003): 141–148.
Nagourney, R. A., B. L. Sommers, S. M. Harper, et al. "Ex vivo Analysis of Topotecan: Advancing the Application of Laboratory-Based Clinical Therapeutics." British Journal of Cancer 89 (November 3, 2003): 1789–1795.
Rasheed, Z. A., and E. H. Rubin. "Mechanisms of Resistance to Topoisomerase I-Targeting Drugs." Oncogene 22 (October 20, 2003): 7296–7304.
Rose, P. G. "Chemotherapy for Newly Diagnosed and Relapsed Advanced Ovarian Cancer." Seminars in Oncology Nursing 19 (November 2003): 25–35.
Organizations
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA (463-6332).
—Marc Scanio; Rebecca J. Frey, PhD
