Mechanism of action and toxicity of cyclophosphamide the immunosuppressive actions of cyclophosphamide are complex. Download fulltext pdf download fulltext pdf cyclophosphamide mechanism of action in preclinical tecemotide studies article pdf available november 20 with 601 reads. Reviewing the chemistry and pharmacology of cyclophosphamide is crucial for understanding its wide therapeutic applicability. Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs. At higher doses, it interrupts cell cycle by forming dna cross linking, dna lesions. Following activation of cyclophosphamide in the liver, multiple metabolites appear in the circulation with varying degrees of immunosuppressive action and toxicity. Results of this study suggest that cyclophosphamide does not impair development of a population of specifically sensitized ttype lymphocytes.
Pdf cyclophosphamide cpa is a nitrogen alkylating agent used for. Cyclophosphamide fda prescribing information, side. Its cytotoxic effect is mainly due to crosslinking of strands of dna and rna, and to inhibition of protein synthesis. Cyclophosphamide is used in combination with busulfan as a conditioning regimen before allogeneic haematopoietic progenitor cell transplantation in patients with chronic myelogenous leukaemia. Mechanism of action of posttransplantation cyclophosphamide. Cyclophosphamide for injection, usp is a sterile white powder containing. Cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide anhydrous. Nov 01, 2019 women treated with cyclophosphamide injection may go through menopause at a younger age than normal. Cyclophosphamide induced sterility may be irreversible in some patients. Tecemotide is a muc1 antigenspecific therapeutic cancer vaccine. Cyclophosphamide is an alkylating agent, and prevents cell division primarily by crosslinking dna and rna strands. Jun 29, 2016 cyclophosphamide interferes with oogenesis and spermatogenesis.
Cytoxan cyclophosphamide for injection, usp cytoxan. Cyclophosphamide can also cause infertility in both men and women. Cyclophosphamide 500 mg powder for solution for injection. The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and. However, several components of the expression phase are affected. Phosphoramide mustard forms dna crosslinks both between and within dna strands at guanine n7 positions known as interstrand and intrastrand crosslinkages, respectively. It is one of the most potent immunosuppressive drugs available. Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions interactions recommended clinical monitoring supplementary public funding references disclaimer. Cyclophosphamide is an alkylating agent of the nitrogen mustard type. Mar 06, 2020 the mechanism of action of cyclophosphamide in autoimmune diseases is thought to involve immunosuppression due to destruction of immune cells via dna crosslinking. Cyclophosphamide is an alkylating cytotoxic drug that is toxic not only to.
Cyclophosphamide has also been used as a single agent in the treatment of lowgrade lymphomas. Cyclophosphamide is used alone or in combination with other medications to treat hodgkins lymphoma hodgkins disease and nonhodgkins lymphoma types of cancer that begin in a type of white blood cells that normally fights infection. Development of sterility appears to depend on the dose of cyclophosphamide, duration of therapy, and the state of gonadal function at the time of treatment. Theres also a slightly increased risk of certain types of cancer, particularly bladder cancer, but cyclophosphamide will not be recommended for you unless the benefits of treatment are thought to be much greater than the risks. Cyclophosphamide cp, also known as cytophosphane among other names, is a medication. Molecular mechanism involved in cyclophosphamideinduced. Cyclophosphamide cyc is an alkylating agent that was introduced into clinical practice as a chemotherapeutic agent but has also been used to treat a number of.
As a single agent for induction therapy, cyclophosphamide is typically given as a dose of 100 mg m. It is a chemotherapy drug that works by slowing or stopping cell growth cyclophosphamide also works by decreasing your immune. Therapeutic use of cyclophosphamide and its cytotoxic action. In high doses, cyclophosphamide affects b cells by inhibiting clonal expansion and suppression of production of immunoglobulins. Cyclophosphamide is a prodrug that is hydroxylated and activated primarily by cyp2b6. Cyclophosphamide is used to treat breast cancer, lung cancer, leukaemia, lymphoma, and myeloma. Inactive ingredients in cyclophosphamide tablets are. Cyclophosphamide is bio transformed principally in the liver to active alkylating metabolites by microsomal oxidase system. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein.
Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. Its prescribed for nonhodgkin lymphoma, hodgkin lymphoma, multiple. Cyclophosphamide 500 mg powder for solution for injection or. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis pdf. Cyclophosphamide can sometimes cause a decrease in your blood count, liver problems, hair loss and mouth ulcers. The mechanism of action is thought to involve crosslinking of tumor cell dna.
The activation mechanism is believed to require an initial oxidative. Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions. Effects of cyclophosphamide on b and tlymphocytes in rheumatoid arthritis. Dailymed cyclophosphamide injection, powder, for solution. Mechanisms of cyclophosphamide action on hepatic p450. Cyclophosphamide in its parent form does not have direct cytotoxic effects.
In the liver, cyclophosphamide is converted to active metabolites including phosphoramide mustard, which binds to and crosslinks dna and rna, thereby inhibiting dna. This treatment resulted in generalized depletion of lymphoid cells, including lymphopenia, and a substantial reduction in the number of macrophages found in induced. The clinical significance of this interaction is unknown. Cyclophosphamide mechanism, indication, contraindications. Pdf cyclophosphamide mechanism of action in preclinical. All of the available evidence indicates that cyclophosphamide exerts its carcinogenic activity via a genotoxic mechanism. The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. Fidanze, in comprehensive medicinal chemistry ii, 2007. Cyclophosphamide mechanism of action in preclinical tecemotide studies ken hance1, robert tighe1, jin qi1, william hastings1, guozhong qin1, bo marelli1, hong wang1, huakui yu1, yanping zhang1, xiaomei xu1, wilson guzman1, masie wong1, giorgio kradjian1, beatrice brunkhorst1, helen sabzevari1, yan lan1, robert hofmeister1, michael wolf2 from. Cyclophosphamide anhydrous is the anhydrous form of cyclophosphamide, a synthetic nitrogen mustard alkylating agent, with antineoplastic and immunosuppressive activities. Cyclophosphamide for injection, usp is a sterile white powder containing cyclophosphamide monohydrate. An activated form of cyclophosphamide, phosphoramide mustard, alkylates, or binds, to dna. Cyclophosphamide is an alkylating drug indicated for treatment of. In phase iii clinical studies, delivery of tecemotide is preceded by a single low dose of cyclophosphamide cpa to inhibit regulatory t cells tregs and enhance the response to the tumorassociated antigen.
Ndechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via cyp3a4. Apr 07, 2014 cyclophosphamide mechanism of action the main effect of cyclophosphamide is due to its metabolite phosphoramide mustard phosphoramide mustard forms dna crosslinks between interstrand crosslinkages and within intrastrand crosslinkages dna strands at guanine n7 position, this eventually leads to cell death 4. Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing. Several studies have examined the mechanism of action of cyclophosphamide. This medicine may cause harm to the unborn baby or loss of the unborn baby if you take it while you are pregnant. These findings establish that cyclophosphamide treatment can modulate hepatic p450 activities through multiple mechanisms and in a manner that may alter p450 metabolism of cyclophosphamide and perhaps other anticancer drugs. Mechanisms of action cyclophosphamide, a nitrogen mustard, is an alkylating agent from the oxazophosphorine group figure 1. Although women taking cyclophosphamide can stop having periods, they can still become pregnant, so an effective form of birth control to prevent pregnancy should be used while taking this medication. Cyclophosphamide injectable solution is a prescription medication used to treat many types of cancer. Cytoxan cyclophosphamide for injection, usp cytoxan tablets. Cyclophosphamide fda prescribing information, side effects. Jun 21, 2019 cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. Cyclophosphamide is used to treat various types of cancer. Mechanisms of cyclophosphamide action on hepatic p450 expression1.
This metabolite is only formed in cells that have low levels of aldh. It is best to read this information with our general information about chemotherapy and the type of cancer you have your doctor will talk to you about this treatment and its possible side effects before you agree consent to have treatment. It is a prodrug that is converted to its active metabolites in liver. This means that the alkylating action of this drug is specifically directed. Taking cyclophosphamide during pregnancy is very dangerous to an unborn child.
A challenge for researchers article pdf available in journal of pharmacy research 48. Pdf therapeutic use of cyclophosphamide and its cytotoxic action. It is transformed via hepatic and intracellular enzymes to active alkylating metabolites. Carcinogenesis, mutagenesis, impairment of fertility. Aldophosphamide undergoes nonenzymatic breakdown into both acrolein and phosphoramide mustard which are also. Cyclophosphamide exhibit the bimodal mechanism of antitumor action with cardiotoxic effect and immunomodulatory effects. Jun 26, 2017 considering the data from human case reports, animal studies and the mechanism of action of cyclophosphamide, its use during pregnancy, in particular during the first trimester, is not recommended. Cyclophosphamide is the generic name of the prescription drug cytoxan, a chemotherapy drug for people with certain cancers.
Cyclophosphamide is a drug that is used primarily for treating several types of cancer. A course of cyclophosphamide administered to guinea pigs after immunization with mycobacteria led to a transient inhibition of cutaneous hypersensitivity to tuberculin protein. Therapeutic use of cyclophosphamide and its cytotoxic. Women must use birth control while taking cyclophosphamide injection and for some time after the last dose. The difference in pharmacological effect depends on the metabolism of the drug, the dose administered, dosing schedule and timing of the dosing. Cyclophosphamide is commonly used with doxorubicin hydroxydaunorubicin, vincristine oncovin, and prednisone known as the chop regimen, with or without other agents, in the treatment of various types of intermediategrade nonhodgkin lymphoma. Caution should be exercised when handling and preparing cyclophosphamide for injection, usp lyophilized powder, or bottles containing cyclophosphamide tablets. Pdf cyclophosphamide mechanism of action in preclinical tecemotide studies find, read and cite all the research you need on researchgate.
Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4hydroxyl metabolites, and shortened t12 values following repeated administration. Over the past 20 years, increased understanding of the mechanism of action of 5fu has led to the development of strategies that. Cyclophosphamide cyc is an alkylating agent that was introduced into clinical practice as a chemotherapeutic agent but has also been used to treat a number of systemic autoimmune diseases. The unchanged drug has an elimination halflife of 3 to 12 hours. It is considered to be cell cycle phasenonspecific. Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn. Rituximab versus cyclophosphamide for ancaassociated. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells. Cyclophosphamide side effects, warnings, dosage, and more. In each individual case the potential benefit of the treatment should be weighed against the potential risk for the foetus. Vb6bearing t cells directed to minor lymphocyte stimu.
A healthcare provider will give you this medication. Acrolein and phosphoramide are the active compounds, and they slow the growth of cancer cells by interfering with the actions of deoxyribonucleic acid dna within the cancerous cells. Cyclophosphamide mechanism of action in preclinical. Jun, 20 cyclophosphamide can cause fetal harm when administered to a pregnant woman based on its mechanism of action and published reports of effects in pregnant patients or animals.
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