Pediatric Osteosarcoma Medication

  • Author: Timothy P Cripe, MD, PhD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Mar 25, 2011
 

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.[23]

In addition, other therapies are being tested, such as the following:[24]

  • Anthracycline escalation using a cardioprotectant[25]
  • Muramyl tripeptide phosphatidyl ethanolamine (MTP-PE)[26] and other immune enhancers (eg interferon)
  • Monoclonal antibody against the Her2/neu antigen, which is overexpressed in some osteosarcomas

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.

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Doxorubicin (Adriamycin, Rubex)

 

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

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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.

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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.

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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.[27]

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Ondansetron (Zofran)

 

Selectively antagonizes serotonin 5-HT3 receptors.

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Dexamethasone (Decadron)

 

Several glucocorticoid and mineralocorticoid effects, including relief of emesis.

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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.

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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.

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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.

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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).

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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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Contributor Information and Disclosures
Author

Timothy P Cripe, MD, PhD  Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD  Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Helen SL Chan, MBBS, FRCP(C), FAAP  Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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Lateral plain radiograph of the knee reveals an osteosarcoma of the distal femur. The lesion is mainly posterior, with disruption and elevation of the periosteum (Codman triangle), and extends beyond the bone into the soft tissue.
Anteroposterior plain radiograph of the same with distal femoral osteosarcoma as shown in image above. The osteolytic lesion is apparent on the right side of the image.
MRI of the same distal femoral osteosarcoma as in images shown under the plain radiography section above; the uninvolved side is shown for comparison.
Close-up MRI of the same distal femoral osteosarcoma as shown in image above, and in images shown under the plain radiography section above.
 
 
 
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