Treatment

If you or a loved one is affected by liver cancer, it is important to know that there may be a team of doctors who will work with you to determine a treatment plan. Physician specialties might include:

Hepatologist/Gastroenterologist that specializes in liver disease
Interventional radiologist
Medical oncologist
Surgeon (transplant surgeon and/or surgical oncologist)

Treatment choices depend on the type and stage of the cancer, how well the liver is functioning and the overall health of the individual.

If the cancer has not spread outside the liver, surgery to remove the tumor or a liver transplant may be considered.^2,9
For more advanced cancers, there are several treatment procedures (see Locoregional Options) that directly damage the liver tumor(s).^2,9
There is also a recently approved oral treatment (see Systemic Therapy) that slows the progression of the cancer.

Surgery

Surgery is the treatment of choice for primary liver cancer. Removing the part of the liver containing the tumor may result in a cure and long-term survival.²

Surgical resection (removal): It may be possible to remove the tumor(s) and the surrounding tissues in the liver if the tumor is small and in one lobe.²
- If the patient has cirrhosis, but still has well-preserved liver function, then resection remains an option.
- However, many patients are not eligible for resection.²
Liver transplant: In patients with small tumors and advanced cirrhosis the treatment of choice is liver transplantation.²

Locoregional Treatment Options^{2, 9}

If the cancer has not spread, but the patient is not well enough to have surgery, procedures that damage or kill the tumor in the liver can be used.

Percutaneous ethanol injection (PEI) can be a useful treatment option in those patients who cannot undergo surgery. This technique is performed under ultrasound guidance. It consists of an injection of alcohol or other substances into the liver, which results in destruction of the tumor.
Radiofrequency ablation (RFA) is the use of high frequency electrical currents to destroy tumor cells. A probe is inserted into or next to a tumor mass and heat from the probe kills the cancer cells in the tumor mass.
Cryosurgery is the use of subzero temperatures to freeze the tumor. Liquid nitrogen is injected directly into the tumor under ultrasound guidance. The tumor is frozen and thawed twice. The procedure can be performed alone or in conjunction with a liver resection.
Transarterial chemoembolization (TACE) is a procedure in which the blood supply to the tumor is blocked and anticancer drugs are administered directly into the tumor. It allows a higher concentration of drugs to be in contact with the tumor for a longer period of time.

Systemic Therapy

Systemic therapy refers to treatment that affects the whole body. In recent years, newer targeted therapies have been developed that target certain protein messengers (kinases) that play a part in the growth and spread of cancer cells and tumors. Research has shown that some kinase signaling pathways inside cancer cells cause them to keep dividing in an uncontrolled fashion causing cancer cells to become tumors. Other important kinase signaling pathways within the surrounding tumor create new blood vessels (neoangiogenesis) which bring the tumor oxygen and nutrients. Therefore these are also important targets to stop the progression and spread of cancer.^{21, 22}

Sorafenib tablets is an oral targeted therapy that has been approved in more than 80 countries to treat patients with HCC. It is the first and only oral treatment for HCC, and has been demonstrated to extend the survival of patients whose tumors cannot be surgically removed, known as unresectable HCC.

How does Sorafenib work?

Sorafenib is designed to interfere with 2 signalling processes on cancer cells and tumor blood vessels.

How sorafenib may work on tumor cells and tumor vessels

By slowing tumor growth and reducing the blood supply of the tumor, targeted therapy may prevent the growth and spread of cancer. These processes can also be important to normal cells, so targeted therapies may affect some normal cells as well.

Essential Information
Name of the medicinal product: Sorafenib; 200 mg film-coated tablets.
Qualitative and quantitative composition: 200 mg sorafenib (as tosylate)
Indication: 1. Treatment of hepatocellular carcinoma. 2. Treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. Contraindications: Hypersensitivity to sorafenib or to any of the excipients. Warnings and Precautions: Hand-foot skin reaction and rash, usually CTC grade 1 and 2. Increased incidence of arterial hypertension (usually mild to moderate, early in the course of treatment). Blood pressure should be monitored regularly and treated as appropriate. Increased risk of bleeding. Increased incidence of cardiac ischaemia/infarction. Gastrointestinal perforation in less than 1%; sorafenib to be discontinued. Levels of sorafenib may be increased in patients with severe hepatic impairment. Infrequent bleeding events or elevations in INR have been reported in some patients taking warfarin concomitantly. Patients on such therapy should be monitored. Temporary treatment interruption and/or dose modification or discontinuation may be considered, depending on the severity of the observed adverse reactions. No formal studies on wound healing have been conducted. Temporary interruption of sorafenib therapy is recommended in patients undergoing major surgical procedures. Experience of use in the elderly is limited and cases of renal failure have been reported. High risk patients according to MSKCC prognostic group were not included in the phase III study in renal cell carcinoma and benefit-risk has not been evaluated in these patients. Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways. Caution is recommended when sorafenib is co-administered with docetaxel. Undesirable effects: Very common: lymphopenia, hypophosphataemia, haemorrhage (incl. gastrointestinal, respiratory tract, cerebral), hypertension, diarrhoea, nausea, vomiting, rash, alopecia, hand-foot syndrome (palmar plantar erythrodysaesthesia syndrome), erythema, pruritus, fatigue, pain (mouth, abdominal, bone, tumour, headache), increased amylase and lipase. Common: leucopenia, neutropenia, anaemia, thrombocytopenia, anorexia, depression, peripheral sensory neuropathy, tinnitus, hoarseness, constipation, stomatitis (including dry mouth and glossodynia), dyspepsia, dysphagia, dry skin, dermatitis exfoliative, acne, skin desquamation, arthralgia, myalgia, renal failure, erectile dysfunction, asthenia, fever, influenza like illness, weight decrease, transient increase in transaminases. Uncommon: folliculitis, infection, hypersensitivity reactions (including skin reactions and urticaria), hypothyroidism, hyponatraemia, dehydration, reversible posterior leukoencephalopathy, myocardial ischaemia and infarction, congestive heart failure, hypertensive crisis, rhinorrhea, gastro oesophageal reflux disease, pancreatitis, gastritis, gastrointestinal perforations, increase in bilirubin, jaundice, cholecystitis, cholangitis, eczema, erythema multiforme minor, keratoacanthoma / squamous cell cancer of the skin, gynaecomastia, increase in alkaline phosphatase, INR abnormality, prothrombin level abnormality. On prescription only.
Date of Revision of the Text: November 2008. Please note! For current prescribing information refer to the package insert and /or contact your local Bayer Schering Pharma Organisation. Bayer Schering Pharma AG, 13342 Berlin, Germany.

For more information about studies being conducted for liver cancer, please visit: www.clinicaltrials.gov.