Antineoplastic agents

Class Summary

Prescribe chemotherapeutic agents only to children with the help of clinicians who are experienced with the doses and toxicities of these drugs. The drugs detailed below are those used in standard CHOP regimen and include cyclophosphamide, hydroxydaunomycin (doxorubicin), vincristine (Oncovin), and prednisone.

Doxorubicin (Adriamycin)

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Alkylating agent with several mechanisms of action (eg, DNA intercalation, topoisomerase-mediated DNA strand breaks, oxidative damage by producing free radicals).

Cyclophosphamide (Cytoxan)

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Exerts cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks and inhibition of DNA replication.

Vincristine (Oncovin)

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Plant-derived vinca alkaloid. Inhibits mitosis by binding tubulin. Inhibits microtubule formation in mitotic spindle, arresting metaphase.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

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Combines ubiquitous uses and likely to downregulate inflammatory proteins by directly signaling with intrachromosomal binding sites.

Class Summary

Antineoplastic-induced vomiting is stimulated through the chemoreceptor trigger zone, which then stimulates the vomiting center in the brain. Increased activity of central neurotransmitters, dopamine in the chemoreceptor trigger zone or acetylcholine in the vomiting center appears to be major mediators for inducing vomiting. After the administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With release of 5-HT and its subsequent binding to 5-HT3-receptors, vagal neurons are stimulated and transmit signals to the vomiting center, resulting in nausea and vomiting.

Antineoplastic agents may cause nausea and vomiting so intolerable that patients may refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents before and after cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.

Ondansetron (Zofran)

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Selective 5-HT3–receptor antagonist that blocks 5-HT peripherally and centrally. Ameliorates chemotherapy-induced nausea and vomiting.

Class Summary

Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide.

In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, which is the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.

Mesna (Mesnex)

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Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.

Follow-up

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