AIDS-Related Lymphomas Medication

Updated: Dec 01, 2015
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications in patients with AIDS-related lymphomas (ARLs).

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Antineoplastic Agents

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

Vincristine (Oncovin, Vincasar PFS)

Vinca alkaloid. Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production.

Etoposide (Toposar, VePesid)

Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks. This causes cell proliferation to arrest in late S or early G2 portion of the cell cycle.

Therapy should be withheld or suspended if platelet counts are < 50,000/μL or absolute neutrophil counts are < 500/mm3. Reduce dose 20% for granulocytic fever or previous radiotherapy. Reduce dose in hepatic (increased total bilirubin [TB]) and renal (decreased CrCl) impairment.

Methotrexate (Folex PFS, Rheumatrex)

Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells.

Cytarabine (Cytosar-U)

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

Has significant activity against systemic lymphoma; half-life in CNS quite long owing to low rates of degradation; therapeutic levels in CSF achieved with high doses; maximally tolerated doses appear to be 3 g/m2, given most effectively as 12-h infusion.

No studies using cytarabine as single agent for PCNSL have been reported; however, has been used as second agent after relapse from MTX chemotherapy.

Cyclophosphamide (Cytoxan, Neosar)

Cyclic polypeptide that suppresses some humoral activity. Chemically related to nitrogen mustards. Activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic.

When used in autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, affects T cell functions.

Adult dose and schedule varies with indication in the management of lymphoma.

Ifosfamide (Ifex)

Chemically related to nitrogen mustards and is a synthetic analogue of cyclophosphamide. Requires metabolic activation in the liver. The alkylated metabolites of ifosfamide have been shown to react with cellular DNA. Inhibits DNA and protein synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of double helix.

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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 (Sterapred, Orasone, Deltasone, Meticorten)

Glucocorticoids have a lympholytic effect, although the mechanism of this action is not clear.

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Colony-stimulating Factors

Class Summary

Colony-stimulating factors increase the activity of neutrophils.

Filgrastim (Neupogen)

Recombinant methionyl human G-CSF (r-metHuG-CSF) consisting of a 175–amino acid protein with a molecular weight of 18,800 d. Produced by Escherichia coli bacteria into which the human G-CSF gene is inserted. This protein has an amino acid sequence identical to the natural sequence predicted from human DNA sequence analysis, except for the addition of an N-terminal methionine necessary for expression in E coli. Because it is produced in E coli, the product is nonglycosylated and thus differs from G-CSF isolated from human cells.

Activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. Acts on precursor cells.

Used to accelerate neutrophil recovery and shorten duration of neutropenic fever. Also indicated to treat patients with chronic neutropenia.

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