Pediatric Osteosarcoma Medication

Updated: Oct 21, 2015
  • Author: Timothy P Cripe, MD, PhD, FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication

Medication Summary

The chemotherapeutic drugs most active in osteosarcoma are doxorubicin, cisplatin, and high-dose methotrexate (for which a low dose is ineffective). Whether chemotherapy dose escalation can improve outcome in patients with a poor histologic response is the subject of an ongoing study in the United States and Europe. One report suggests that, although dose intensification increases the number of patients with a good histologic response, it does not change overall survival. [27]

As usual, physicians caring for patients with osteosarcoma should consult a pediatric oncologist affiliated with a center that participates in national or international trials to determine both the current standard treatment protocol and whether an appropriate investigational study is open for patient accrual.

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Antineoplastic agents

Class Summary

These agents disrupt DNA replication or cell division, thereby inhibiting tumor growth and promoting the death of tumor cells.

Doxorubicin (Adriamycin, Rubex)

Mechanisms of action include DNA intercalation, topoisomerase-mediated DNA strand breaks, and oxidative damage by means of free-radical production.

Cisplatin (Platinol, CDDP)

Mechanism of action is platination of DNA, mechanism analogous to alkylation leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

Methotrexate (Folex PFS, high dose)

Folate analog. Competitively inhibits dihydrofolate reductase, inhibiting DNA replication and RNA transcription; patients should receive adequate hydration and alkalinization to ensure effective drug clearance.

Ifosfamide (Ifex)

DNA alkylator, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA synthesis.

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Antiemetic agents

Class Summary

Emesis is a clinically significant adverse effect of chemotherapeutic drugs, particularly the drugs used to treat osteosarcoma. Patients often require several antiemetics, and antiemetic regimens should be tailored for each patient. Commonly used antiemetics include serotonin receptor antagonists (eg, dolasetron, granisetron, ondansetron, tropisetron), corticosteroids (eg, dexamethasone), and dopamine receptor antagonists (eg, metoclopramide, prochlorperazine). The American Society of Clinical Oncology published evidence-based clinical practice guidelines for the use of antiemetics used for chemotherapy-induced nausea and vomiting. [28]

Ondansetron (Zofran)

Selectively antagonizes serotonin 5-HT3 receptors.

Dexamethasone (Decadron)

Dexamethasone elicits glucocorticoid effects and has minimal-to-no mineralocorticoid effects. The antiemetic mechanism for corticosteroids is unknown, but inhibition of prostaglandin synthesis and cell membrane permeability are thought to be involved. Dexamethasone is used in combination with other antiemetic agents.

Prochlorperazine (Compazine)

Selectively antagonizes dopamine D2 receptors.

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Colony-stimulating factors

Class Summary

These agents act as hematopoietic growth factors that stimulate development of granulocytes. They are used to treat or prevent neutropenia when a patient is receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation.

Filgrastim (Neupogen)

Granulocyte colony-stimulating factor (G-CSF) that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. Shortens time to recovery of neutrophils after chemotherapy by stimulating bone marrow production of neutrophil precursors. Also stimulates granulocytic antibacterial functions.

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Antidotes

Class Summary

These agents are used to manage poisoning and overdose, prevent toxic effects, or treat metabolic disorders in which toxic substances accrue. Mechanisms of action vary and include antagonism, toxin transformation, altered metabolism, chelation, and directed antibody responses.

Leucovorin (Wellcovorin)

Also called citrovorum factor or folinic acid. Overrides folate antagonist (methotrexate) and protects against severe methotrexate-induced toxic effects. Discontinue when serum methotrexate level < 10-7 mol/L.

Dexrazoxane (Zinecard)

Preventatively used as cardioprotectant to reduce incidence and severity of anthracycline cardiotoxicity; therefore, raises maximum tolerated dose. Exact mechanism unknown. Derivative of ethylenediaminetetraacetic acid (EDTA) and potent intracellular chelating agent. May interfere with iron-mediated free-radical generation that may be partly responsible for anthracycline-induced cardiomyopathy. Dose determined by the doxorubicin dose (ie, 10X doxorubicin dose).

Mesna (Mesnex)

Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. Used as prophylactic detoxifying agent to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide. In kidney, mesna disulfide reduced to free mesna, which has thiol groups that react with acrolein, the ifosfamide or cyclophosphamide metabolite considered responsible for urotoxicity.

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