Pediatric Hodgkin Lymphoma Medication

Updated: Mar 20, 2017
  • Author: Pedro A de Alarcon, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP  more...
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Medication

Medication Summary

Several chemotherapeutic agents in various combinations are used to treat Hodgkin lymphoma (HL). The combinations vary by the stage of disease and by the treating institution. In patients with relapsing or unresponsive disease, autologous 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 non overlapping 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.

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Antineoplastic Agents

Class Summary

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 cancers grow quickly and undergo cell division more often compared with normal tissues, and the growth rate may be decreased in large tumors. This difference makes cancer more susceptible to chemotherapy.

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.

Mechlorethamine (Mustargen)

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

Bleomycin

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

Vinblastine

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

Dacarbazine

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

Etoposide (Toposar)

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

Vincristine ( Vincasar PFS)

Vincristine is a vinca alkaloid with a mechanism of action similar to that of vinblastine.

Procarbazine (Matulane)

Procarbazine is an alkylating agent with mechanism of action similar to that of dacarbazine.

Prednisone

Prednisone is a corticosteroid used to treat leukemias and lymphomas because of its lympholytic activity.

Cyclophosphamide

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.

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.

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, Antimetabolite

Class Summary

These agents inhibit cell growth and proliferation.

Gemcitabine (Gemzar)

Gemcitabine is a cytidine analog. It is metabolized intracellularly to an active nucleotide. It inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. It is cell-cycle specific for the S phase and inhibits DNA synthesis by inhibiting DNA polymerase.

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Antineoplastics, Monoclonal Antibody

Class Summary

The agents in this class target specific antigens in carcinoma cells and induce cytotoxicity.

Brentuximab vedotin (Adcetris)

Brentuximab vedotin is an antibody genetically engineered antibody drug conjugate directed at DC30 consisting of a CD30-specific chimeric IgG1 antibody cAC10, a microtubule-disrupting agent, and a protease-cleavable dipeptide that conjugates MMAE to cAC10. The antibody internalizes MMAE within the cells, which then disrupts the microtubule network, causing cell cycle arrest and apoptosis.

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PD-1/PD-L1 Inhibitors

Class Summary

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.

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. Efficacy for pediatric patients is extrapolated from the results in the adult cHL population.

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