Sections

Medication

Medication Summary

All chemotherapy orders are written and countersigned by pediatric oncologists. Most children are treated according to clinical protocols used in multiple institutions. For patients with refractory disease, a phase I or II trial is usually considered. Information on clinical trials is usually accessible through the National Cancer Institute (NCI) Web site and linked sites. The resources presented below should serve as guidelines only.

Antineoplastic agents have a narrow therapeutic index, and effective doses usually cause significant toxic effects. Any physician or other practitioner caring for children with cancer must be familiar with the indications, appropriate dosages, and toxic effects of the chemotherapy agents prescribed. They must also be familiar with any special considerations regarding age, weight, pharmacokinetic variations (ie, drug absorption, distribution, metabolism, excretion), coexisting medical problems, or possible pharmacokinetic interactions. To minimize risk to the patient, only practitioners familiar with the toxic effects and potential complications should prescribe antineoplastic agents.

Full discussion of the agents typically used in treating hepatoblastoma is beyond the scope of this article, but brief summaries of the drugs most commonly used are provided below.

Class Summary

The mechanism of action is similar to that of alkylating agents, namely, binding and cross-linking DNA strands.

Carboplatin (Paraplatin)

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Similar to cisplatin, produces DNA cross-links that are predominantly interstrand. Effect is cell cycle nonspecific.

Cisplatin (Platinol)

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Binds and cross-links DNA strands, disrupting cell function. Usually combined with etoposide or doxorubicin.

Cyclophosphamide (Cytoxan, Neosar)

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After metabolism by hepatic microsomal enzymes, produces active alkylating metabolites that probably damage DNA. Usually administered with doxorubicin and vincristine or doxorubicin and cisplatin. Also an immunosuppressant.

Administered with mesna to prevent urotoxicity (ie, hemorrhagic cystitis).

Class Summary

These agents are usually derived from microorganisms and have various antitumor mechanisms. All interfere with the DNA structure or the breakage-resealing process.

Doxorubicin (Adriamycin)

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Causes DNA strand breakage mediated by effects on topoisomerase II. Intercalates into DNA and inhibits DNA polymerase. Usually combined with vincristine and cyclophosphamide, or with cisplatin.

Class Summary

These plant alkaloids inhibit the topoisomerases that interfere with the normal DNA breakage-resealing reaction and cause single-strand breaks in DNA.

Etoposide (Toposar, VePesid)

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Interacts with topoisomerase II and produces single-strand breaks in DNA. Arrests cells in late S phase or G₂ phase. Typically combined with ifosfamide, cisplatin, or carboplatin.

Class Summary

These agents are close structural analogs of vital intermediates in the biosynthetic pathways of nucleic acids and proteins. They either inhibit synthesis of cellular macromolecules and their building blocks or are incorporated into the macromolecules, resulting in a defective product.

5-Fluorouracil (Adrucil)

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Prodrug that inhibits thymidine synthesis and is incorporated into RNA and DNA.

Specific to the S phase of the cell cycle.

Class Summary

These plant alkaloids bind to microtubular proteins, inhibiting RNA synthesis by disrupting DNA formation.

Vincristine (Oncovin, Vincasar PFS)

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Binds tubulin, leading to its depolymerization, which results in mitotic inhibition and metaphase arrest. Specific to S and M phases of the cell cycle. Used in combination with doxorubicin and cyclophosphamide.

Class Summary

These agents promote growth and differentiation of myeloid progenitor cells. They may improve survival and function of granulocytes.

Filgrastim (Neupogen)

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G-CSF Used to combat neutropenia, particularly in patients receiving myelosuppressive therapy. Produced recombinantly in Escherichia coli for clinical use.

Follow-up

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Media Gallery

Clear cell hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
Embryonal hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
Fetal components of hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
Hepatoblastoma. Normal liver tissue. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.

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Author

Arun A Rangaswami, MD Professor of Clinical Pediatrics, Division of Hematology-Oncology, University of California, San Francisco, School of Medicine

Arun A Rangaswami, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, Children's Oncology Group

Disclosure: Nothing to disclose.

Coauthor(s)

Gary Dahl, MD Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine

Gary Dahl, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group

Disclosure: Nothing to disclose.

Tara Anne Laureano, RN, MSN, FNP-C Family Nurse Practitioner in Pediatric Oncology, Bass Center for Childhood Cancer and Blood Disorders, Lucile Packard Children's Hospital at Stanford

Tara Anne Laureano, RN, MSN, FNP-C is a member of the following medical societies: American Association of Nurse Practitioners, California Association for Nurse Practitioners

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Stanford Children's Hospital Pediatric Oncology.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD 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, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

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

Disclosure: Nothing to disclose.

Additional Contributors

Stephan A Grupp, MD, PhD Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, Society for Pediatric Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Alexandra (Lowry) Abrams, MD Associate Medical Director, George Mark Children’s House

Disclosure: Nothing to disclose.

Acknowledgements

The authors would like to thank all of our patients and families, as well as all of our mentors along this path towards a better outcome for children with hepatoblastoma!

Pediatric Hepatoblastoma Medication

Medication Summary

Antineoplastic agents, alkylating agents, metal salts

Class Summary

Carboplatin (Paraplatin)

Carboplatin (Paraplatin)

Cisplatin (Platinol)

Cisplatin (Platinol)

Cyclophosphamide (Cytoxan, Neosar)

Cyclophosphamide (Cytoxan, Neosar)

Antitumor antibiotics, natural products

Class Summary

Doxorubicin (Adriamycin)

Doxorubicin (Adriamycin)

Topoisomerase II inhibitors, natural products

Class Summary

Etoposide (Toposar, VePesid)

Etoposide (Toposar, VePesid)

Antineoplastic antimetabolites

Class Summary

5-Fluorouracil (Adrucil)

5-Fluorouracil (Adrucil)

Mitotic inhibitors, natural products

Class Summary

Vincristine (Oncovin, Vincasar PFS)

Vincristine (Oncovin, Vincasar PFS)

Colony-stimulating factors

Class Summary

Filgrastim (Neupogen)

Filgrastim (Neupogen)

Pediatric Hepatoblastoma Medication

Medication Summary

Antineoplastic agents, alkylating agents, metal salts

Class Summary

Carboplatin (Paraplatin)

Cisplatin (Platinol)

Cyclophosphamide (Cytoxan, Neosar)

Antitumor antibiotics, natural products

Class Summary

Doxorubicin (Adriamycin)

Topoisomerase II inhibitors, natural products

Class Summary

Etoposide (Toposar, VePesid)

Antineoplastic antimetabolites

Class Summary

5-Fluorouracil (Adrucil)

Mitotic inhibitors, natural products

Class Summary

Vincristine (Oncovin, Vincasar PFS)

Colony-stimulating factors

Class Summary

Filgrastim (Neupogen)

References

Tables

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