Diffuse Large Cell Lymphoma Medication

Updated: Feb 07, 2016
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to induce cancer remission, reduce morbidity, and prevent complications.

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Antineoplastics, Other

Class Summary

These agents inhibit cell growth and proliferation.

Cyclophosphamide

Cyclophosphamide has antineoplastic activity mediated by its 2 active metabolites. These metabolites are alkylating agents that prevent cell division by cross-linking DNA strands. Cyclophosphamide is absorbed almost completely from the GI tract, making it bioavailable in either oral (PO) or intravenous (IV) forms. Excretion is primarily via urine.

Doxorubicin (Adriamycin)

Doxorubicin is an anthracycline antibiotic that can intercalate with DNA, affecting many of the functions of DNA, including synthesis. This agent is administered intravenously. Doxorubicin distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. It does not cross the blood-brain barrier, and it is excreted primarily in bile.

Vincristine (Vincasar PFS)

Vincristine is a vinca alkaloid that is cell cycle specific (M phase). The mitotic apparatus is arrested in metaphase via disruption of the microtubules. Absorption of vincristine through the GI tract is variable; therefore, administer the drug intravenously. It is metabolized extensively in the liver and excreted primarily via bile. Neurotoxicity is the limiting factor during therapy. Peripheral neuropathy is vincristine's most common adverse effect at usual doses.

Etoposide (Toposar)

Etoposide is an epipodophyllotoxin that induces DNA strand breaks by disrupting topoisomerase II activity.

Cisplatin

Cisplatin is a platinum-containing compound that exerts its antineoplastic effect by covalently binding to DNA with preferential binding to N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to cause cross-links. The platinum complex also can bind to the nucleus and cytoplasmic protein. Cisplatin is a bifunctional alkylating agent that once activated to an aquated form in the cell, binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of the double helix.

Cytarabine

Cytarabine is converted intracellularly to the active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. It is cell cycle S phase specific. Cytarabine blocks the progression from the G1 to the S phase and, in turn, kills cells that undergo DNA synthesis in the S phase of the cell proliferation cycle.

Bleomycin

Bleomycin is a group of glycopeptides extracted from Streptomyces species. Each molecule has a planar end and an amine end; different glycopeptides of the group differ in their terminal amine moieties. The planar end intercalates with DNA, while the amine end facilitates oxidation of bound ferrous ions to ferric ions, thereby generating free radicals, which subsequently cleave DNA, acting specifically at purine-G-C-pyrimidine sequences.

Carboplatin

Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to action of these drugs in the G1 and S phases.

Carboplatin has the same efficacy as cisplatin but with a better toxicity profile. The main advantages over cisplatin include less nephrotoxicity and ototoxicity, thus not requiring extensive prehydration, and it is less likely to induce nausea and vomiting; however, it is more likely to induce myelotoxicity.

Ifosfamide (Ifex)

Ifosfamide binds with nucleic acids and other intracellular structures, causing cross-linking of DNA strands. It inhibits DNA and protein synthesis.

Mechlorethamine (Mustargen)

This alkylating agent is a component of the MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen.

Methotrexate (Rheumatrex, Trexall)

Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, which is necessary for conversion of folate to biologically active tetrahydrofolate.

Procarbazine (Matulane)

Procarbazine is an alkylating agent that inhibits DNA, RNA, and protein synthesis. It inhibits cell replication in all phases of the cell cycle.

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.

Prednisone

Prednisone is a glucocorticoid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability. Prednisone is readily absorbed via the GI tract and is metabolized in the liver. Inactive metabolites of prednisone are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose or duration dependent.

Dexamethasone (Baycadron)

A component of the m-BACOD regimen (methotrexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, Oncovin, and dexamethasone), dexamethasone is a corticosteroid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.

Dexamethasone is readily absorbed via the GI tract and is metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.

Methylprednisolone (Depo-Medrol, Solu-Medrol, Medrol, A-Methapred)

A component of the ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), methylprednisolone is a corticosteroid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.

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Monoclonal Antibodies

Class Summary

Monoclonal antibodies are antibodies targeted to specific antigenic determinants. They can be specific to growth factors, cytokines, and cell surface molecules found on tumor cells.

Rituximab (Rituxan)

The rituximab antibody is a genetically engineered chimeric mouse/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and neoplastic B lymphocytes.

The most common adverse reactions to rituximab are infusion reactions, some of which are fatal. Bowel perforation has been reported with rituximab. Patients reporting abdominal pain during therapy should be evaluated for perforation of the intestinal tract.

Reactivation of hepatitis B has been demonstrated; patients at high risk for hepatitis B should be screened prior to initiation of therapy. No studies have been conducted to determine if a dose adjustment is necessary in patients with hepatic or renal dysfunction.

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Colony-Stimulating Factors Growth Factor

Class Summary

These agents can induce an increase in reticulocyte counts with a subsequent increase in hematocrit and hemoglobin levels.

Epoetin alfa (Epogen, Procrit)

Epoetin alfa is a purified glycoprotein produced from mammalian cells modified with gene coding for human erythropoietin (EPO). Its amino acid sequence is identical to that of endogenous EPO, and its biological activity mimics human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from bone marrow into the blood stream.

Darbepoetin alfa (Aranesp)

Darbepoetin alfa is an erythropoiesis-stimulating protein closely related to erythropoietin, a primary growth factor produced in the kidneys that stimulates the development of erythroid progenitor cells. Its mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase red blood cell production. Darbepoetin alfa differs from epoetin alfa (recombinant human erythropoietin) in that it contains 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3. Darbepoetin alfa has a longer half-life than epoetin alfa (may be administered weekly or biweekly).

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Vitamins

Class Summary

Vitamins are used to correct folic acid deficiency resulting from use of folic acid antagonists.

Leucovorin

Leucovorin is used with folic acid antagonists, such as methotrexate. It is a reduced form of folic acid that does not require enzymatic reduction reaction for activation. It allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. It is an important cofactor for the enzymes used in the production of red blood cells. Leucovorin (folinic acid, which reduces adverse effects) is given on alternating days with methotrexate, until there is a 15% decline in β-HCG over 2 days.

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Antidotes, Other

Class Summary

These agents counteract the toxic effects of drugs.

Mesna (Mesnex)

In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. It inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. The adult dosage is 240 mg IV at 0, 4, 8 hours after the ifosfamide or cyclophosphamide dose.

Mesna may increase warfarin effects. Mesna does not prevent hemorrhagic cystitis in all patients (monitoring for hematuria in the morning prior to ifosfamide or cyclophosphamide dose is required). It does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide. Common adverse effects include hypotension, headache, GI toxicity, and limb pain. Mesna is a pregnancy category B drug.

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Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of trimethoprim/sulfamethoxazole includes common urinary tract pathogens, except Pseudomonas aeruginosa.

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Antifungals, Other

Class Summary

An antifungal may be used in the ProMACE-CytaBOM regimen. The mechanism of action may involve the inhibition of pathways (eg, enzyme, substrate, transport) that are necessary for sterol and/or cell membrane synthesis.

Ketoconazole (Extina, Xolegel)

Imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.

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Antiemetics

Class Summary

Antiemetics are always prescribed before and after the administration of chemotherapy, for the prevention of chemotherapy-induced nausea and vomiting.

Ondansetron (Zofran, Zuplenz)

Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.

Granisetron (Kytril, Granisol, Sancuso)

At the chemoreceptor trigger zone, granisetron blocks serotonin centrally and peripherally on vagal nerve terminals.

Palonosetron (Aloxi)

Palonosetron is a selective 5-HT3 receptor antagonist with a long half-life (40 h). It is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.

Metoclopramide (Reglan, Metozolv)

The antiemetic effect of metoclopramide appears to be the result of its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS). This agent also enhances gastrointestinal motility and accelerates gastric emptying time.

Prochlorperazine (Compro)

Prochlorperazine may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and by depressing the reticular activating system.

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