Hepatocellular Carcinoma Treatment Protocols 

Updated: Aug 02, 2021
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment Protocols

Treatment protocols for hepatocellular carcinoma (HCC) are provided below. Historically, HCC treatment protocols have been divided into two broad categories: for resectable and unresectable disease. In addition, special considerations include bridge therapy for patients awaiting transplant and combination therapies. [1]

Treatment recommendations for patients with early-stage resectable disease

See the list below:

  • For patients with early-stage HCC, a partial hepatectomy can offer a potential cure, provided the patient is a surgical candidate, based on performance status and comorbidities. [2]

  • Hepatic resection is recommended in patients who have preserved liver function (generally Child-Pugh class A without portal hypertension) and a solitary mass without macrovascular invasion, and who will have an adequate liver remnant.

  • For patients with limited disease, but deemed unresectable due to tumor characteristics and location, liver transplantation may offer an alternative option for curative treatment.

Treatment recommendations for patients with unresectable disease (including those with disease limited to liver and those with advanced disease)

Treatment regimens for patients with limited disease confined to the liver, limited to no macrovascular invasion, and no metastatic disease, are as follows:

  • For patients with unresectable disease, liver transplantation should be offered to those who are surgical candidates and meet United Network for Organ Sharing (UNOS) criteria (ie, a single tumor ≤ 5 cm in diameter or 2-3 tumors, each ≤ 3 cm in diameter; no evidence of major vascular involvement and no extrahepatic disease) [3]
  • For patients with unresectable disease who are not surgical candidates because of their performance status, comorbidities, and failure to meet UNOS criteria, National Comprehensive Cancer Network (NCCN) guidelines recommend offering locoregional therapies before initiating systemic treatment.

  • Locoregional therapies comprise ablation, arterially directed therapies, and radiation therapy, [2]

  • Ablative procedures include radiofrequency, cryoablation, percutaneous alcohol injection, and microwave/thermal ablation. Tumor size and location is the limiting factor in offering this approach.

  • Arterially directed therapies include bland transarterial embolization (TAE), transarterial chemoembolization (TACE), TACE with drug-eluting beads (DEB-TACE), and radioembolization (RE) with yttrium-90 microspheres. Elevated bilirubin level > 3 mg/dL is a relative contraindication to this approach.

  • Radiation therapies include intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and external-body radiation therapy (EBRT). This therapy can be offered both for treatment and palliation. 

The following treatment regimens are used for patients with advanced disease no longer confined to the liver, major vascular involvement, and/or metastatic disease; this may include patients who are not candidates for locoregional therapies and/or those in whom local treatment has failed.

First-line systemic treatment for unresectable HCC

Sorafenib is administered as follows:

  • 400 mg PO BID (common practice is to start at 200 mg daily, increase to 200 mg BID, then escalate to 400 mg BID) [4, 5]
  • For moderate liver dysfunction, use 200 mg PO BID
  • Use with extreme caution in patients with elevated bilirubin levels [6]

Lenvatinib is administered until disease progression or unacceptable toxicity occurs. The dose is based on actual body weight, as follows [7] :

  • < 60 kg: 8 mg PO once daily
  • ≥ 60 kg: 12 mg PO once daily

Bevacizumab is administered in combination with atezolizumab as follows [8, 9] :

  • Bevacizumab 15 mg/kg IV on Day 1 (after administration of atezolizumab) plus
  • Atezolizumab 1,200 mg/kg IV on Day 1
  • Repeat every 3 weeks
  • Continue until disease progression or unacceptable toxicity

Options for patients previously treated with sorafenib:

  • Regorafenib 160 mg PO once daily for the first 21 days of each 28-day cycle; continue treatment until disease progression or unacceptable toxicity [10]
  • Nivolumab 240 mg IV plus  ipilimumab 3 mg/kg IV every 3 weeks (4 doses), followed by nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression or unacceptable toxicity  [11]
  • Pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression [12, 13]
  • Cabozantinib 60 mg PO once daily without food until disease progression or unacceptable toxicity [14]
  • Ramucirumab 8 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity [15]

The NCCN notes that only limited data support the use of chemotherapy, and use in the context of a clinical trial is preferred. [2] However, the following regimens have shown marginal activity in small clinical trials:

  • Gemcitabine 1000 mg/m2 IV on day 1 plus oxaliplatin 100 mg/m2 on day 2; then every 14d [16, 17] or

  • Capecitabine 1000 mg/m2 PO BID on days 1-14 plus  oxaliplatin 130 mg/m2 IV on day 1; then every 21d [18] or

  • Capecitabine 1000 mg/m2 PO BID on days 1-14; then every 21d [19] or

  • Doxorubicin 60-75 mg/m2 IV on day 1; then every 21d [20, 21] or

  • Gemcitabine 1250 mg/m2 IV on days 1 and 8 plus cisplatin 35 mg/m2 IV on days 1 and 8; then every 21d [22, 23]