Treatment Options for Liver Cancer

Palliative Treatments for Liver Cancer

A variety of palliative treatments are available for patients with localized, unresectable liver cancer that cannot be removed surgically due to either the location of the tumor within the liver, poor liver function, or other underlying health problems. The term "localized" refers to the confinement of the cancer to the area of the liver without evidence of spread to the lymph nodes or other areas of the body. As mentioned previously, palliative treatments for liver cancer are not curative but rather are intended to control the disease and prevent further progression, thereby, prolonging survival.

Palliative treatments for liver cancer include:

• Radiofrequency thermal ablation
• Percutaneous ethanol injection
• Cryosurgery
• Hepatic arterial embolization
• Systemic chemotherapy
• Hormonal therapy
• Radiation therapy

Radiofrequency Thermal Ablation

Radiofrequency thermal ablation is a technique that is used to destroy the tumor with high-energy radiofrequency waves. During this procedure, the surgeon inserts a special probe called a radiofrequency electrode directly into the tumor with the assistance of imaging guidance such as ultrasound, CT, or MRI. Various surgical techniques can be used to insert the electrode into the tumor including percutaneously (through the skin), laparoscopically, or by performing a laparotomy (creating an open incision into the abdomen). Once the probe has been placed into the tumor, radiofrequency energy is applied that heats up the electrode and causes destruction of the tumor. In general, radiofrequency thermal ablation is used for the treatment of localized, unresectable nodular-type liver tumors that are 3.0 to 5.0 cm in size. Complications of this technique, which may develop in less than 10% of patients, include fever, pain, irregular heart beats, bleeding, and formation of liver abscess.

Percutaneous Ethanol Injection

Another commonly used technique used for treating patients with localized, unresectable liver cancer is called percutaneous ethanol injection (PEI). In this technique, the surgeon uses ultrasound guidance to insert a small needle into the tumor and then injects absolute ethanol directly into the tumor to destroy the cancer cells. Multiple treatments (usually 4 to 8 sessions) are required to shrink the liver tumor and the procedure is repeated once or twice weekly. This procedure is performed on an outpatient basis under local anesthesia. In general, PEI is useful for the treatment of smaller (3.0 cm or less) nodular liver cancer tumors and is usually recommended for patients with three or fewer tumors. The most common side-effects of PEI are fever and pain which usually resolve within a few days after the procedure. The estimated 5-year survival rate for PEI has been reported to range from 30% to 60%.

Cryosurgery

Another technique that is sometimes used to destroy liver tumors is known as cryosurgery. This procedure involves placing a probe containing liquid nitrogen into the tumor and destroying the cancer cells by exposing them to freezing temperatures. Potential complications of cryosurgery include hypothermia (low body temperature), bleeding, irregular heart beats, kidney failure, and bile duct injury.

Hepatic Arterial Embolization

This is one of the most widely used palliative treatments for patients with localized, unresectable liver cancer. The basic goal of hepatic arterial embolization is to deprive the tumor of its blood supply by embolization (occlusion) of the hepatic artery which supplies blood to the tumor. Once the blood supply to the tumor has been cut-off, the cancer cells die and the tumor shrinks.

In performing this procedure, the surgeon inserts a tube called a catheter into the hepatic artery and then injects tiny gelatin particles into the artery to block the flow of blood. In some cases, anticancer drugs, such as doxorubicin, mitomicin C, or cisplatin, may also be injected into the hepatic artery along with the gelatin particles. This type of localized cancer treatment is known as chemoembolization and results in very high local concentrations of anticancer drugs at the tumor site for a prolonged period of time. Although hepatic arterial embolization, with or without chemotherapy, is not a curative treatment for liver cancer, it does confer benefits by slowing down the rate of tumor progression and, thereby, prolonging survival. Because patients with poor liver function cannot eliminate (detoxify) the high concentrations of anticancer drugs that are used during chemoembolization, this treatment modality is usually restricted to patients with adequate residual liver function.

Systemic Chemotherapy

Some patients with advanced-stage liver cancer, where the cancer has spread throughout the liver or to other parts of the body, receive systemic chemotherapy with anticancer drugs in an attempt to slow the progression of the disease and prolong survival. Unfortunately, liver cancer does not respond well to most forms of standard systemic chemotherapy. Because many patients with advanced-stage liver cancer also have extensive liver cirrhosis and poor residual liver function, the use of systemic chemotherapy in these patients is even more challenging and problematic.

The anticancer drug that is most widely used as systemic chemotherapy for liver cancer is doxorubicin (Adriamycin). Combination chemotherapy with several different drugs may also be used. Some of the drugs that may be used in combination chemotherapy include doxorubicin, cisplatin, 5-fluorouracil, and tegafur.

In general, most studies have not demonstrated an improvement in survival rates with either single-agent or combination chemotherapy in patients with advanced-stage liver cancer.

In November 2007, the U.S. Food and Drug Administration (FDA) approved a drug called sorafenib (Nexavar) for use in patients with hepatocellular carcinoma when the cancer is inoperable. Sorafenib, which is a member of a class of drugs known as tyrosine kinase inhibitors that was originally approved in 2005 for the treatment of patients with advanced renal cell carcinoma (the most common form of kidney cancer. Sorafenib is formulated as a tablet and is taken by patients orally (by mouth).

The FDA's approval of sorafenib was based on the results of an international randomized, controlled clinical trial involving 602 patients with inoperable hepatocellular carcinoma which showed a statistically significant benefit in terms of survival for patients treated with sorafenib. Patients in the study who received sorafenib survived and average of 10.7 months compared to only 7.9 months for patients who received a placebo. The tumor progression rate among patients who were treated with sorafenib was also slower than for the group of patients who received a placebo.

The most common adverse reactions reported for patients who have been treated with sorafenib are:

• Abdominal pain
• Anorexia
• Diarrhea
• Fatigue
• Hair loss
• Nausea
• Skin rash
• Weight loss

Side-Effects of Chemotherapy

A drawback of chemotherapy for the treatment of cancer is that it can produce a variety of undesired side-effects. The side-effects of chemotherapy vary depending upon the type of drug(s) used, the dosage, and the length of time that the chemotherapy is administered. In general, common side-effects of cancer chemotherapy may include:

• Hair loss
• Mucositis - Inflammation of the lining of the mouth and gastrointestinal tract, which can be very painful.
• Increased susceptibility to infections
• Increased susceptibility to bleeding and bruising
• Fatigue and general feeling of weakness
• Nausea and vomiting
• Loss of appetite

The side-effects of cancer chemotherapy are temporary and usually disappear after treatment has been completed. A variety of strategies are available to better control the side-effects of chemotherapy and patients should discuss with their oncologist the various options that can be used to minimize or reduce these adverse side-effects.

Hormonal Therapy

The presence of hormone receptors on the surface of cancer cells in some patients with advanced-stage liver cancer provided the rationale for attempting to use anti-hormonal therapy to slow the progression of the disease. Tamoxifen hormonal therapy has been used successfully for the treatment of some types of breast cancer (estrogen-receptor positive breast cancer). Unfortunately, clinical trials of tamoxifen for the treatment of advanced-stage liver cancer have been disappointing and have not shown a benefit in terms of increasing survival. Other forms of hormonal therapy, including a variety of antiandrogens and aromatose inhibitors (eg., anastrozole) are currently being investigated.

Radiation Therapy

External beam radiation therapy uses high-energy beams of radiation from a special machine called a linear accelerator to direct radiation to a tumor. External beam radiation therapy may sometimes be used as a means of alleviating pain in patients with liver cancer but is rarely used as a primary mode of treatment for liver cancer. In some cases, doctors may inject a radioactive isotope directly into the hepatic artery (the primary blood supply to liver tumors) in an attempt to shrink the tumor. This form of radiation therapy is called local radiation therapy. Once injected into the hepatic artery, the radioactive isotope is transported via the bloodstream to the site of the liver tumor where it emits high doses of energy to kill the cancer cells. The most common radioactive isotopes used for local radiation therapy of liver cancer include iodine-131 Lipiodol and Yttrium-90 microspheres. Unfortunately, neither external beam radiation nor local radiation therapy has shown significant benefits in terms of survival in patients with liver cancer.