Hodgkin Lymphoma Medication

Updated: Sep 13, 2018
  • Author: Bradley W Lash, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

Medication Summary

Several chemotherapeutic agents in various combinations are used to treat Hodgkin lymphoma. The combinations vary by the stage of disease and by the treating institution. In patients with relapsing or unresponsive disease, hematopoietic stem-cell transplantation significantly prolongs disease-free survival. Various drug combinations have been used with stem-cell rescue.

Although the intended target is the malignant cells of Hodgkin lymphoma, the effects of chemotherapy on normal cells of the body are considerable and account for the adverse effects observed with these agents. Because most patients with Hodgkin lymphoma are long-term survivors, one of the goals of current therapy is to decrease the long-term adverse effects while maintaining excellent cure rates. The use of different therapeutic agents with nonoverlapping toxicities is one way to achieve this goal. Various combinations of the drugs presented below are used to treat Hodgkin lymphoma .

Although adverse effects vary with each drug, some are common to many drugs. These adverse effects include nausea, vomiting, alopecia, bone marrow suppression, and, less commonly, secondary malignancies.

Cancer chemotherapy is based on an understanding of tumor cell growth and of how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2), then finally a mitotic cell division (ie, phase M).

Cell-division rates vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the growth rate may be decreased in large tumors. This difference allows normal cells to recover more quickly than malignant ones after chemotherapy and is the rationale behind current cyclic dosage schedules.

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Antineoplastics, Alkylating

Class Summary

Antineoplastic agents interfere with cell reproduction. Some agents are specific to phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.

Alkylating antineoplastic agents elicit their effects through the formation of covalent bonds with DNA, which disturbs protein synthesis and cellular division. They are able to form bonds with DNA of all cells, especially those which reproduce rapidly. Because of their nonspecific action on cells, toxicities to normal cells are an issue.

Mechlorethamine (Mustargen)

Mechloroethamine is a component of the MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen. It exerts cytotoxic effect by inhibiting rapid proliferation of cancer cells.

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Antineoplastics, Antibiotic

Class Summary

Antibiotic antineoplastic agents are produced by microorganisms and inhibit or prevent the proliferation of neoplasms.

Bleomycin (Blenoxane)

Classified as an antibiotic, bleomycin induces free radical-mediated breaks in strands of DNA. This agent is part of the ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) regimen.

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Antineoplastics, Vinca Alkaloid

Class Summary

The vinca alkaloid agents are naturally occurring or semisynthetic nitrogenous bases that elicit their cytotoxic effects through tubulin-binding properties and disruption of microtubule function, which lead to metaphase arrest.

Vinblastine (Velban)

Vinblastine is a vinca alkaloid that inhibits mitosis because of interactions with tubulin.

Dacarbazine (DTIC-Dome)

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

Vincristine (Vincasar PFS, Oncovin)

Vincristine is a vinca alkaloid with a mechanism of action similar to that of vinblastine. It is presumed to stop the metaphase stage therefore preventing microtubule formation in the mitotic spindle.

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Antineoplastics, Podophyllotoxin Derivatives

Class Summary

Podophyllotoxin derivative antineoplastic agents have cytotoxic effects on cell growth.

Etoposide (Toposar)

Etoposide is an epipodophyllotoxin that induces DNA strand breaks by disrupting topoisomerase II activity. This causes cell proliferation to arrest in the late S or early G2 portion of the cell cycle.

Procarbazine (Matulane)

Procarbazine is an alkylating agent with a mechanism of action similar to that of dacarbazine: inhibition of DNA, RNA, and protein synthesis. It inhibits cell replication in all phases of the cell cycle. It is part of COPP, BEACOPP and MOPP regimens.

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Antineoplastics, Alkylating, DMARDs, Immunomodulators

Class Summary

Cyclophosphamide is a synthetic agent similar to nitrogen mustard. This agent requires activation in the liver to form its active intermediaries, which in turn modify and cross-link DNA, thereby inhibiting DNA, RNA, and protein synthesis. Eventually, apoptosis occurs.

Cyclophosphamide (Cytoxan)

Cyclophosphamide is an alkylating agent that is chemically related to nitrogen mustards. The mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

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Immunosuppressants; Antineoplastics, Antimetabolite; DMARDs, Immunomodulators

Class Summary

Antimetabolite antineoplastic agents interfere with cell functions by competing for its receptors or enzymes involved in the synthesis of DNA. Tissues that have a high rate of cellular metabolism are most sensitive to the effects.

Methotrexate (Rheumatrex, Trexall)

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

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Antineoplastics, Anthracyclines

Class Summary

Anthracycline antineoplastic agents elicit their cytotoxic effects through nucleotide base intercalation and cell membrane lipid-binding. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases.

Doxorubicin (Adriamycin)

An anthracycline that functions as a DNA intercalator, doxorubicin inhibits topoisomerase II and produces free radicals, which may destroy DNA. The combination of these 2 events can inhibit the growth of neoplastic cells. Doxorubicin is administered intravenously and distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. It does not cross the blood-brain barrier and is excreted primarily in bile.

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Antineoplastics, Antimicrotubular

Class Summary

Antimicrotubular antineoplastics disrupt the microtubular network in cells by promoting stabilization and assembly. In addition, these agents block the disassembly of microtubules, thereby preventing cell division, leading to cell death.

Brentuximab vedotin (Adcetris)

Brentuximab is a CD30-directed antibody-drug conjugate (ADC) that consists of chimeric IgG1 antibody cAC10, which is specific for human CD30, bound to the microtubule-disrupting agent monomethyl auristatin E (MMAE, or vedotin). This agent is indicated for treatment of classic Hodgkin lymphoma (cHL) after failure of autologous stem cell transplant (ASCT) or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It is also indicated as consolidation treatment post-auto-HSCT in patients with high risk for relapse or disease progression. Additionally, brentuximab vedotin is indicated as first-line therapy for previously untreated stage III-IV cHL in combination with chemotherapy.

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PD-1/PD-L1 Inhibitors

Class Summary

Immunotherapy is emerging for use in hematologic malignancies.

PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions. PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound.

This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation.

Nivolumab (Opdivo)

Monoclonal antibody which inhibits suppression of T-cells by blocking the interaction between programmed cell death-1 protein and its ligands. Nivolumab is indicated for the treatment of classical Hodgkin lymphoma in patients who have relapsed or shown progression after autologous hematopoietic stem cell transplantation (HSCT) and post transplantation brentuximab vedotin.

Pembrolizumab (Keytruda)

Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. It is indicated for adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL) or who have relapsed after 3 or more prior lines of therapy.

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Corticosteroids

Class Summary

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

Prednisone (Deltasone)

Prednisone is a corticosteroid used to treat leukemias and lymphomas because of its lympholytic activity. Prednisone 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 gastrointestinal tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.

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