Liver Cancer (cont.)
Keith E. Stuart, MD
Keith E. Stuart, MD
Dr. Keith E. Stuart is a medical oncologist specializing in the study and treatment of cancers involving the gastrointestinal tract, with a special interest in tumors involving the liver. He was educated at Harvard University (graduating magna cum laude) and Albert Einstein College of Medicine and did his medical training at the New England Deaconess Hospital.
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
In this Article
Chemotherapy and biotherapy
Systemic (entire body) chemotherapy
The most commonly used systemic chemotherapeutic agents are doxorubicin (Adriamycin) and 5-fluorouracil (5 FU). These drugs are used together or in combination with new experimental agents. These drugs are quite toxic and results have been disappointing. A few studies suggest some benefit with tamoxifen (Nolvadex) but more studies show no advantage at all. Octreotide (Sandostatin) given as an injection was shown in one study to slow down the progression of large liver cancer tumors, but so far, no other studies have confirmed this benefit. Recent studies suggest that combinations of drugs such as gemcitabine, cisplatin, or oxaliplatin can shrink the tumors in some people.
One of the most important recent advances in the filed of treating liver cancer has been the understanding of the genetic makeup of these tumors, as well as the cancer cells' reliance upon blood vessels and molecules produced in the body that can help them grow. Many cancers grow by causing the development and recruitment of tiny new blood vessels to feed the tumor and enable it to spread to other parts of the body. This is called angiogenesis, and this has become a very hot field in oncology and pharmaceutical development over the past decade. One drug, bevacizumab, has been approved for use in many cancers such as colon, lung, and breast, and is known to help standard chemotherapy shrink and control other types of cancer. It might be helpful in liver cancer as well, and similar drugs are still being investigated.
The best success so far has been with the oral drug sorafenib (Nexavar). This is a pill designed to block several components of the angiogenesis pathway, as well as other growth signals for individual cancer cells. Large studies have shown that patients taking this drug for advanced liver cancer live significantly longer than those taking a placebo pill. Although the difference was not very long (three months) and is shorter in sicker patients, this is still the first study in decades to show that there is a reliable way to slow down this cancer's growth and to prolong patients' lives. Sorafenib is thus the first, and so far, only, drug to be approved by the U.S. FDA to treat liver cancer. Current studies are under way to see if the drug works better when combined with other types of chemotherapy.
Hepatic arterial infusion of chemotherapy
The normal liver gets its blood supply from two sources: the portal vein (about 70%) and the hepatic artery (30%). However, liver cancer gets its blood exclusively from the hepatic artery. Making use of this fact, investigators have delivered chemotherapy agents selectively through the hepatic artery directly to the tumor. The theoretical advantage is that higher concentrations of the agents can be delivered to the tumors without subjecting the patients to the systemic toxicity of the agents.
In reality, however, much of the chemotherapeutic agents does end up in the rest of the body. Therefore, selective intra-arterial chemotherapy can cause the usual systemic (body-wide) side effects. In addition, this treatment can result in some regional side effects, such as inflammation of the gallbladder (cholecystitis), intestinal and stomach ulcers, and inflammation of the pancreas (pancreatitis). Liver cancer patients with advanced cirrhosis may develop liver failure after this treatment. Well then, what is the benefit of intra-arterial chemotherapy? The bottom line is that fewer than 50% of patients will experience a reduction in tumor size.
An interventional radiologist (one who does therapeutic procedures) usually carries out this procedure. The radiologist must work closely with an oncologist (cancer specialist), who determines the amount of chemotherapy that the patient receives at each session. Some patients may undergo repeat sessions at six- to 12-week intervals. This procedure is done with the help of fluoroscopy (a type of X-ray) imaging. A catheter (long, narrow tube) is inserted into the femoral artery in the groin and is threaded into the aorta (the main artery of the body). From the aorta, the catheter is advanced into the hepatic artery. Once the branches of the hepatic artery that feed the liver cancer are identified, the chemotherapy is infused. The whole procedure takes one to two hours, and then the catheter is removed.
The patient generally stays in the hospital overnight for observation. A sandbag is placed over the groin to compress the area where the catheter was inserted into the femoral artery. The nurses periodically check for signs of bleeding from the femoral artery puncture. They also check for the pulse in the foot on the side of the catheter insertion to be sure that the femoral artery is not blocked as a result of the procedure. (Blockage would be signaled by the absence of a pulse.)
Generally, the liver enzyme tests increase (get worse) during the two to three days after the procedure. This worsening of the liver tests is actually due to death of the tumor (and some non-tumor) cells. The patient may experience some post-procedure abdominal pain and low-grade fever. However, severe abdominal pain and vomiting suggest that a more serious complication has developed. Imaging studies of the liver are repeated in six to 12 weeks to assess the size of the tumor in response to the treatment. For more, please read the chemotherapy article.
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