eMedicine Specialties > Pediatrics: General Medicine > Oncology
Hepatocellular Carcinoma: Treatment & Medication
Updated: Feb 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Hepatocellular carcinoma (HCC) is most easily treated in its earliest stages of presentation. Because patients often present with advanced disease, for which treatment modalities are limited at best, recent emphasis has been placed on screening for hepatocellular carcinoma in at-risk patients. Patients with chronic hepatitis B have a relative risk for developing hepatocellular carcinoma that is 100-fold greater than that of uninfected persons. Currently, patients with chronic hepatitis B or C are recommended to have an annual a- fetoprotein level obtained. If the level is 29 ng/mL or more, continued surveillance is recommended at least annually.
Ultrasonography is also recommended at similar intervals for patients who are at risk. Suspicious lesions warrant biopsy; however, in patients who are found to have a lesion larger than 2 cm and an a- fetoprotein level in excess of 200 ng/mL, biopsy may not be necessary because the chance of hepatocellular is virtually 100% in these cases.
Surgical Care
Surgical resection must be undertaken by a surgeon familiar with liver tumor management. Underlying coagulation defects may complicate the surgery. Pathologic analysis that shows no remaining cells is the goal of resection. Although the liver is capable of regeneration, overly aggressive resection may predispose the patient to liver failure and death. Transarterial embolization and chemoembolization have been used with limited success.Consultations
Management by a pediatric oncology healthcare team is required. This team should include individuals from the following areas of specialty: surgery, psychiatry, radiation oncology, infectious disease, metabolic disorders, diagnostic radiology, pharmacy, nursing specialists, and social work.
Diet
Vitamin K supplementation may help patients with a coagulation defect.
Activity
Activity depends on the overall health of the individual after surgery or chemotherapy.
Medication
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 cyclophosphamide2
- 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.3
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.
Antineoplastic agents
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.
Adult
25 mg/m2 IV push or continuous infusion on days 1-3 (total dose 75 mg/m2/72 h
Pediatric
Administer as in adults
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin
Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Irreversible cardiac toxicity and grade III and IV myelosuppression may occur; mucositis; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function
Cisplatin (Platinol)
A planar, inorganic compound that interacts with DNA. The mechanism of action is to cause intrastrand crosslinks that interfere with replication.
Adult
45 mg/m2/d IV infused over 4-6 h on days 1-2 (total dose 90 mg/m2/48 h)
Pediatric
20-40 mg/m2/d IV for 5 d
Alternative: 90-100 mg/m2 IV as a single dose
Requires prehydration and should be administered with 0.45% NaCl, potassium chloride, and mannitol
Increases toxicity of bleomycin and ethacrynic acid; cyclosporine may increase CNS toxicity
Documented hypersensitivity, preexisting renal insufficiency, myelosuppression, and hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May produce significant nephrotoxicity and ototoxicity; CrCl and audiologic evaluation must be performed at baseline and during the course of therapy to monitor renal function and hearing; other primary toxic effects include nausea, vomiting (highly emetogenic), myelosuppression, electrolyte disturbances; rare toxic effects include metallic taste, peripheral neuropathy, hepatotoxicity, and secondary leukemia; close monitoring of CBC count and platelets is necessary
Patients must avoid exposure to ill contacts, seek care for fever or bleeding, and avoid contact sports
5-Fluorouracil (5FU; Adrucil)
Prodrug inhibits thymidine synthesis and is incorporated into RNA and DNA. Specific to the S phase of the cell cycle.
Adult
15 mg/kg/d IV continuous infusion (over 24 h) for 5 consecutive d
Pediatric
500 mg/m2 IV push as single dose or qd for 5 d; or 800-1200 mg/m2 continuous IV infusion over 24–120 h
No guidelines available for modifying dose in patients with hepatic or renal dysfunction
Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents
Clearance delayed and toxicity increased by thymidine competing for enzyme that catabolizes 5-FU; intracellular activation and incorporation into RNA increased by methotrexate
Documented hypersensitivity; inherited deficiency of catabolic enzyme dihydropyrimidine dehydrogenase (associated with severe 5-FU toxicity); bone marrow suppression, serious infection
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Toxic effects exacerbated by impairments in liver function
Dose-limiting toxic effects include leukopenia and thrombocytopenia, severe diarrhea, stomatitis, and dysphagia; local ulceration if extravasation occurs; other common toxic effects include proctitis, nausea and vomiting, partial loss of nails, hypopigmentation, and immunosuppression; severe mucositis can lead to infection, dehydration, and poor nutritional status; close monitoring of CBC count is necessary
Patients must avoid exposure to ill contacts and seek care for fever or bleeding
Antiemetics
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).
Adult
24-32 mg/d PO/IV
Pediatric
0.45 mg/kg/d; up to 24-32 mg/d PO/IV
Although there is potential for CYP-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance of ondansetron, dosage adjustment usually is not required
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Headache occurs commonly; total daily dose should not exceed 8 mg/d for patients with severe liver failure
More on Hepatocellular Carcinoma |
| Overview: Hepatocellular Carcinoma |
| Differential Diagnoses & Workup: Hepatocellular Carcinoma |
 Treatment & Medication: Hepatocellular Carcinoma |
| Follow-up: Hepatocellular Carcinoma |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
hepatocellular carcinoma, hepatoma, HCC, fibrolamellar carcinoma, malignant hepatoma, hepatocarcinoma, liver cell carcinoma, liver disease, liver dysfunction, parenchymal cells, liver, tumor, cancer, cirrhosis, hepatitis B, hepatitis C, hemochromatosis, Gaucher disease, Gaucher's disease, biliary atresia, infantile cholestasis, glycogen-storage disease, cirrhosis, hepatitis B, hepatitis C, liver dysfunction, tyrosinemia, pleural effusions
