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.
Antineoplastic agents, alkylating agents, metal salts
Class Summary
The mechanism of action is similar to that of alkylating agents, namely, binding and cross-linking DNA strands.
Carboplatin (Paraplatin)
Similar to cisplatin, produces DNA cross-links that are predominantly interstrand. Effect is cell cycle nonspecific.
Cisplatin (Platinol)
Binds and cross-links DNA strands, disrupting cell function. Usually combined with etoposide or doxorubicin.
Cyclophosphamide (Cytoxan, Neosar)
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).
Antitumor antibiotics, natural products
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)
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.
Topoisomerase II inhibitors, natural products
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)
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.
Antineoplastic antimetabolites
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)
Prodrug that inhibits thymidine synthesis and is incorporated into RNA and DNA.
Specific to the S phase of the cell cycle.
Mitotic inhibitors, natural products
Class Summary
These plant alkaloids bind to microtubular proteins, inhibiting RNA synthesis by disrupting DNA formation.
Vincristine (Oncovin, Vincasar PFS)
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.
Colony-stimulating factors
Class Summary
These agents promote growth and differentiation of myeloid progenitor cells. They may improve survival and function of granulocytes.
Filgrastim (Neupogen)
G-CSF Used to combat neutropenia, particularly in patients receiving myelosuppressive therapy. Produced recombinantly in Escherichia coli for clinical use.
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Clear cell hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
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Embryonal hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
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Fetal components of hepatoblastoma. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
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Hepatoblastoma. Normal liver tissue. Hematoxylin and eosin stain. Image courtesy of Denise Malicki, MD.
