Which medications in the drug class Antineoplastics are used in the treatment of Acute Lymphoblastic Leukemia (ALL)?

Updated: Jun 20, 2019
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Antineoplastics

Antineoplastic agents are used for induction, consolidation, maintenance, and central nervous system (CNS) prophylaxis.

Cancer chemotherapy is based on an understanding of tumor cell growth and 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 rate may be decreased in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones and is the rationale behind current cyclic dosage schedules.

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

Vincristine (Vincasar PFS)

Vincristine is a vinca alkaloid agent that acts by arresting cells in metaphase.

Vincristine liposomal (Marqibo)

A sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine. Indicated for treatment of Ph-negative ALL for patients in second or greater relapse or whose disease has progressed following 2 or more antileukemia therapies.

Asparaginase Erwinia chrysanthemi (Erwinaze)

Catalyzes deamidation of asparagine to aspartic acid and ammonia, thereby reducing circulating levels of asparagine. Lack of asparagine synthetase activity results in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine. Indicated as part of a multiagent chemotherapeutic regimen as a substitute for asparaginase (Elspar), which was discontinued by the manufacturer in August 2012.

Pegaspargase (Oncaspar)

Modified version of L-asparaginase. Selective killing of leukemic cells it thought to be due to depletion of plasma asparagine, the amino acid required for protein synthesis. It is indicated as a component of a multi-agent chemotherapeutic regimen for the first line treatment of ALL. It is also indicated for use in patients with hypersensitivity to native forms of L-asparaginase.

Methotrexate (Trexall, Xatmep, Otrexup, Rasuvo)

Methotrexate is an antimetabolite of the folic acid analogue type. This agent inhibits dihydrofolate reductase, resulting in inhibition of DNA synthesis, repair, and cellular replication.

Mercaptopurine (Purinethol)

Mercaptopurine is antimetabolite of the purine analogue type. Its primary effect is inhibition of DNA synthesis.

Cyclophosphamide

Cyclophosphamide is an alkylating agent of the nitrogen mustard type that acts by inhibiting cell growth and proliferation.

Cytarabine

Cytosine arabinoside is an antimetabolite that induces activity as a result of activation to cytarabine triphosphate and includes inhibition of DNA polymerase and incorporation into DNA and RNA.

Daunorubicin (Cerubidine)

Daunorubicin is an anthracycline that inhibits topoisomerase II. This agent also inhibits DNA and RNA synthesis by intercalating between DNA base pairs.

Idarubicin (Idamycin)

Idarubicin is a topoisomerase II inhibitor that inhibits cell proliferation by inhibiting DNA and RNA polymerase.

Mitoxantrone (Novantrone)

Mitoxantrone is also a topoisomerase II inhibitor. This agent inhibits cell proliferation by intercalating DNA and inhibiting topoisomerase II.

Nelarabine (Arranon)

Nelarabine is a prodrug of the deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (ara-G) that is converted to the active 5'-triphosphate, ara-GTP, a T-cell–selective nucleoside analogue. Leukemic blast cells accumulate ara-GTP, which allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death.

This agent is approved by the US Food and Drug Administration (FDA) as an orphan drug to treat persons with T-cell ALL whose disease has not responded to or which has relapsed with at least 2 chemotherapy regimens.

Clofarabine (Clolar)

Clofarabine is a purine nucleoside antimetabolite that inhibits DNA synthesis and is indicated for relapsed or refractory acute lymphoblastic leukemia in pediatric patients. Pools of cellular deoxynucleotide triphosphate are decreased by inhibiting ribonucleotide reductase and terminating DNA chain elongation and repair. This agent also disrupts mitochondrial membrane integrity. It is indicated for the treatment of patients aged 1-21 years who have relapsed or refractory acute ALL. For adults older than 21 years, base dosing on surface area as in pediatrics. Clofarabine is not indicated for adults older than 21 years.

Inotuzumab (Besponsa)

Inotuzumab is a CD22-directed antibody-drug conjugate (ADC) indicated for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Recognizes human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic agent which covalently attaches to antibody via a linker. Data suggest anticancer activity of inotuzumab ozogamicin is due to binding of ADC to CD22-expressing tumor cells, followed by internalization of ADC-CD22 complex, and ultimately activating N-acetyl-gamma-calicheamicin 19 dimethylhydrazide, which induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death.


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