Pediatric Hepatocellular Carcinoma Medication

Updated: Nov 05, 2015
  • Author: Paulette Mehta, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication

Medication Summary

Unfortunately, complete surgical resection of hepatocellular carcinoma (HCC) is possible in fewer than 30% of children at diagnosis. Hepatocellular carcinoma is only partially chemosensitive; thus, chemotherapy and radiation have limited efficacy as adjuvant or neoadjuvant therapy, although one or both are often used to temporarily control disease. In patients who are chemosensitive, chemotherapy may allow a meaningful reduction in tumor size before surgical control, in some cases rendering unresectable tumors resectable. Several combination chemotherapy regimens have been used.

One widely used regimen in children is doxorubicin and cisplatin (PLADO). Resectability rate and, hence, survival rate is higher among children who respond to neoadjuvant chemotherapy compared with children who do not. [1]

Alternative regimens include the following:

  • Ifosfamide, carboplatin, and etoposide (ICE)

  • 5-Fluorouracil in combination with vincristine, Adriamycin, and cyclophosphamide [3]

  • Gemcitabine and carboplatin (recently gained acceptance as potentially active against hepatocellular carcinoma)

Recent trials in adults have demonstrated the efficacy of tyrosine kinase inhibitors like sorafenib in patient with locally advanced hepatocellular carcinoma. The efficacy and safety of these therapeutic measures in children remains to be determined. [4, 5]

Chemoembolization into isolated branches of the hepatic artery may benefit patients with nonmetastatic but unresectable or recurrent tumor. This is the more commonly used approach in adults, in whom systemic chemotherapy has had essentially no impact on disease-free survival.

Because the liver plays a key role in chemically inactivating many chemotherapeutic agents, the child with an underlying liver disease or extensive hepatic involvement with hepatocellular carcinoma warrants careful observation. Numerous reports associate hepatic coma with chemotherapy initiation.

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Antineoplastic agents

Class Summary

Chemotherapy is used for tumor size reduction to allow for subsequent resection, in the setting of positive resection margins after surgery, and as palliation in the setting of advanced regional or metastatic disease.

When given postoperatively, chemotherapy is usually initiated approximately 4 weeks after surgery to allow liver regeneration. A minimum of 2 weeks should pass after surgery before administration of cytotoxic agents.

These drugs have achieved partial response rates in patients. Although suggested doses are supplied, these doses widely vary among protocols, and the information cannot be used to design patient treatment plans.

Doxorubicin (Adriamycin, Rubex)

An anthracycline antibiotic derived from Streptomyces peucetius susp caesius. Doxorubicin is a DNA-intercalating agent that interferes with DNA and RNA synthesis.

Cisplatin (Platinol)

A planar, inorganic compound that interacts with DNA. The mechanism of action is to cause intrastrand crosslinks that interfere with replication.

Fluorouracil

Prodrug inhibits thymidine synthesis and is incorporated into RNA and DNA. Specific to the S phase of the cell cycle.

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Antiemetics

Class Summary

Antineoplastic induced vomiting is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of central neurotransmitters, dopamine in CTZ, or acetylcholine in VC appears to be a major mediator for inducing vomiting. Following administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With serotonin release and subsequent binding to 5-HT3–receptors, vagal neurons are stimulated and transmit signals to the VC, 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 following cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.

The 5-HT antagonists are highly effective at controlling cisplatin-induced nausea.

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin).

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