What are the treatment protocols for advanced hepatocellular carcinoma (HCC)?

Updated: Jun 05, 2020
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Answer

Answer

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 every 2 weeks or 480 mg IV every 4 weeks, until disease progression or unacceptable toxicities [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 toxicities [14]
  • Ramucirumab 8 mg/kg IV every 2 weeks until disease progression or unacceptable toxicities [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]


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