Clinical data | |
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Pronunciation | /ˌɛtoʊˈpoʊsaɪd/ |
Trade names | Etopophos, Toposar, Vepesid, others |
Other names | VP-16; VP-16-213 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a684055 |
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Routes of administration | By mouth, intravenous |
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Pharmacokinetic data | |
Bioavailability | Highly variable, 25 to 75% |
Protein binding | 97% |
Metabolism | Liver (CYP3A4 involved) |
Elimination half-life | Oral: 6 h., IV: 6-12 h., IV in children: 3 h. |
Excretion | Kidney and fecal |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.046.812 |
Chemical and physical data | |
Formula | C29H32O13 |
Molar mass | 588.562 g·mol−1 |
3D model (JSmol) | |
Melting point | 243.5 °C (470.3 °F) |
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Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. [2] It is also used for hemophagocytic lymphohistiocytosis. [3] It is used by mouth or injection into a vein. [2]
Side effects are very common. [2] They can include low blood cell counts, vomiting, loss of appetite, diarrhea, hair loss, and fever. [2] Other severe side effects include allergic reactions and low blood pressure. [2] [4] Use during pregnancy will likely harm the fetus. [2] Etoposide is in the topoisomerase inhibitor family of medication. [2] It is believed to work by damaging DNA. [2]
Etoposide was approved for medical use in the United States in 1983. [2] It is on the World Health Organization's List of Essential Medicines. [5]
Etoposide is used as a form of chemotherapy for cancers such as Kaposi’s sarcoma, Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs (such as bleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant. [6]
It is given intravenously (IV) or orally in capsule or tablet form. If the drug is given IV, it must be done slowly over a 30- to 60-minute period because it can lower blood pressure as it is being administered. [2] Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.[ citation needed ]
Common are:
Less common are:
Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, which is an enzyme that aids in relaxing negative or positive supercoils in DNA. Topoisomerase II normally will form a double-stranded break in one DNA double-strand, allow another to pass through, and re-ligate the broken strands. Etoposide's binding prevents topoisomerase II from re-ligating the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension. [8] Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell. [6] [9]
Etoposide is a semisynthetic derivative of podophyllotoxin from the rhizome of the mayapple (or "American mandrake", Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a D-glucose derivative. It is chemically similar to the anti-cancer drug teniposide, being distinguished only by a methyl group where teniposide has a thienyl. [10] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin. [11]
The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents. [11]
It is used in form of its salt etoposide phosphate.
Etoposide was first synthesized in 1966 and U.S. Food and Drug Administration approval was granted in 1983. [6]
The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (von Wartburg) and podophyllotoxin. [12] Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.
Chemotherapy is the type of cancer treatment that uses one or more anti-cancer drugs in a standard regimen. Chemotherapy may be given with a curative intent, or it may aim only to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
DNA topoisomerases are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in DNA arise due to the intertwined nature of its double-helical structure, which, for example, can lead to overwinding of the DNA duplex during DNA replication and transcription. If left unchanged, this torsion would eventually stop the DNA or RNA polymerases involved in these processes from continuing along the DNA helix. A second topological challenge results from the linking or tangling of DNA during replication. Left unresolved, links between replicated DNA will impede cell division. The DNA topoisomerases prevent and correct these types of topological problems. They do this by binding to DNA and cutting the sugar-phosphate backbone of either one or both of the DNA strands. This transient break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed. Since the overall chemical composition and connectivity of the DNA do not change, the DNA substrate and product are chemical isomers, differing only in their topology.
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and decreases the number of attacks. It is taken by mouth.
Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.
Daunorubicin, also known as daunomycin, is a chemotherapy medication used to treat cancer. Specifically it is used for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma. It is administered by injection into a vein. A liposomal formulation known as liposomal daunorubicin also exists.
Azacitidine, sold under the brand name Vidaza among others, is a medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
Podophyllum peltatum is an herbaceous perennial plant in the family Berberidaceae. Its common names are mayapple, American mandrake, wild mandrake, and ground lemon. It is widespread across most of the eastern United States and southeastern Canada.
Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocarcinoma; and uveal melanoma. It is taken by mouth or by injection into a vein.
Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisplatin. It is given intravenously.
Teniposide is a chemotherapeutic medication used in the treatment of childhood acute lymphocytic leukemia (ALL), Hodgkin's lymphoma, certain brain tumours, and other types of cancer. It is in a class of drugs known as podophyllotoxin derivatives and slows the growth of cancer cells in the body.
Podophyllotoxin (PPT) is the active ingredient in Podofilox, which is a medical cream that is used to treat genital warts and molluscum contagiosum. It is not recommended in HPV infections without external warts. It can be applied either by a healthcare provider or the person themselves.
Chlorambucil, sold under the brand name Leukeran among others, is a chemotherapy medication used to treat chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and non-Hodgkin lymphoma. For CLL it is a preferred treatment. It is given by mouth.
Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.
Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death. Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.
Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change the linking number of circular DNA by ±2. Topoisomerases are ubiquitous enzymes, found in all living organisms.
Epipodophyllotoxins are substances naturally occurring in the root of American Mayapple plant.
Hartmann F. Stähelin was a Swiss pharmacologist with an outstanding record in basic and applied cancer and immunology research. He discovered two important drugs: etoposide and ciclosporin.
DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene.
Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.
Plant sources of anti-cancer agents are plants, the derivatives of which have been shown to be usable for the treatment or prevention of cancer in humans.