Etoposide is a chemotherapy agent that is used in combination with other therapies to treat several types of cancer. It is approved by the U.S. Food and Drug Administration (FDA) to treat testicular cancer and small cell lung cancer. The therapy also can be used to treat myeloma.
How does etoposide work?
Myeloma is a type of blood cancer that begins in the bone marrow, the spongy tissue inside some bones, such as the hip and thigh bones. The cancerous cells divide quickly and spread from one location to another.
Etoposide is a therapy derived from a toxin present in the Mayapple plant. It binds to and blocks the activity of an enzyme called topoisomerase 2.
In order for a cell to divide, it must make a complete copy of its DNA so that each new cell has a copy. This is called DNA replication. During this process, the two strands of DNA need to be separated. This can cause the DNA to coil around itself and tangle as it is pulled apart. Topoisomerase 2 cuts the DNA to release the tension and then repairs the DNA break.
By binding to topoisomerase 2 and blocking its activity, etoposide causes the enzyme not to be able to rejoin the cuts in the DNA, which leads to DNA damage. In cancerous cells — which divide much more rapidly than normal cells — this damage quickly becomes cumulative, stopping the cell from dividing and leading to cell death.
Etoposide in clinical trials
The therapy is used as part of a treatment combination called DCEP — for dexamethasone, cyclophosphamide, etoposide, and cisplatin.
A study published in JBUON, the Journal of the Balkan Union of Oncology, tested the treatment combination in 12 patients with relapsed or refractory multiple myeloma who had failed 4-to-6 cycles of other chemotherapy regimens. Seven of the 12 participants were candidates for autologous hematopoietic stem cell transplantation (AHSCT), in which a patient’s own cells are collected, treated in the lab, and then returned to the body. The DCEP therapy was given in a 24-hour infusion in the first four days of a 28-day treatment cycle. The corticosteroid dexamethasone also was given on days 1 to 4. The dosage of cisplatin, a platinum-containing chemotherapy agent, was adjusted for patients who demonstrated a reduction in kidney function. A growth factor, which is an essential preparation for AHSCT, was given from day 5 until recovery. The treatment course was repeated every 28 days.
The results of the study showed the treatment combination was well-tolerated. After two cycles, two of the 12 patients achieved complete remission, five showed partial remission, and the remaining five showed no response. The overall response rate was 58.3%. Four patients went on to successful AHSCT therapy.
Etoposide also has been shown to increase cellular mobilization in preparation for AHSCT in myeloma patients.
A study published in Biology of Blood and Marrow Transplantation investigated the efficacy and safety of etoposide in combination with a growth factor treatment to mobilize cells for AHSCT. A total 152 myeloma patients were enrolled in that study.
The combination of the etoposide and the growth factor resulted in mobilization in all the patients. Adverse effects of the therapy included transfusions required in 20% of patients, and fevers requiring hospitalization in 17% of patients. The researchers concluded that etoposide and growth factors are a safe and effective cell mobilization regimen for people with myeloma.
Etoposide treatment can cause side effects that include increased risk of infection, thrombocytopenia or low blood platelet counts, anemia, loss of appetite, constipation, and sore throat. It also can lead to peripheral neuropathy, causing numbness or tingling in the hands or feet.
Regular blood cell counts are often required during treatment with etoposide.
Last updated: Mar. 3, 2020
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