NEWS

New Treatments Target Metastatic Tumors in Liver

Joyce Baldwin

The treatment of colorectal cancer and other cancers that have metastasized to the liver presents a set of unique issues. Surgical resection of the tumor is the established gold standard against which newer therapies are compared, but only a small percentage of patients are candidates for surgery, and there are clear risks associated with resection.

New techniques and chemotherapy agents are in clinical trials specifically for the 70% to 90% of patients with metastatic colon cancer who are not candidates for surgery.

About half of patients with colorectal cancer either have liver metastases at the time of diagnosis or go on to develop hepatic metastases. Although long-term survival rates associated with resectable disease have improved to 30% or 40%, researchers hope that new techniques can improve that statistic.

"A combination of surgery, new techniques in ablation, and certainly better chemotherapy will make a difference in long-term survival," said David A. Iannitti, M.D., assistant professor of surgery at Brown University School of Medicine in Providence, R.I. "We already are making a difference, but what the best combination will be, we don’t know yet. New agents are continually being developed, and we’re conducting new trials constantly."

One technique that can specifically target metastases in the liver is cryotherapy—using either a liquid nitrogen or argon gas system to freeze tumors to as low as minus 180 degrees Celsius. Trials of cryotherapy have demonstrated that complete ablation of metastases in the liver from colon cancer is associated with five-year survival rates of 20% to 25%. (See News, Sept. 20, 2000, p. 1464.)

However, cryotherapy is usually done operatively, and there are risks associated with the procedure. Bleeding, which occurs when the frozen area cracks, can be severe; other risks include the development of lung problems and hypothermia.

Radiofrequency Ablation

Radiofrequency ablation (RFA), a newer ablation technique, destroys tumors using needle probes that heat lesions up to 80 degrees or 90 degrees Celsius. The procedure can usually be done percutaneously on an outpatient basis.

At the eighty-second annual meeting of the New England Surgical Society last September, Iannitti reported data on 123 patients with metastatic colorectal cancer, hepatocellular carcinoma (HCC), or other types of cancer who underwent 168 RFA sessions over a two-and-a-half-year period. Of the patients with colorectal metastases, 87% survived for 1 year, 77% for 2 years, and 50% for 3 years. The patients with HCC had somewhat higher survival rates of 92%, 75%, and 60% for 1, 2, and 3 years, respectively.

Using RFA percutaneously, it is possible to treat a few small lesions at one time; several lesions or larger lesions require operative ablation. An open procedure allows more thorough evaluation of the liver with intraoperative ultrasound and thus is more likely to result in complete ablations, Iannitti said. Lesions near the diaphragm or near the stomach, colon, or gall bladder also require surgery in conjunction with RFA.

Since the U.S. Food and Drug Administration just approved RFA in 1997, there is no information on 5-year survival rates following the procedure. When these data are available, Iannitti said he expects they will be comparable to or exceed those associated with cryoablation.

"I think RFA is going to be a little bit better than cryoablation," said Iannitti, who has worked with both techniques. "When you are cooking a tumor and it’s smoking and bubbling and popping, you know that you are completely killing it." He added that these data might not appear to be quite as good as those for cryoablation because most RFA procedures are done percutaneously, and it is possible to miss some lesions that might be found with intraoperative ultrasound. Iannitti and his colleagues will launch a clinical trial this year to directly compare surgical resection with RFA in patients with colon cancer that has spread to the liver.

Brachytherapy

Another new technique for inoperable liver cancer is a type of brachytherapy that delivers radioactive yttrium-90 directly to the liver via millions of glass beads that measure about 25 to 35 microns in diameter. The beads are trapped in the tumor, where they release beta rays directly at the tumor.

Andrew Kennedy, M.D., reported at the November meeting of the Radiological Society of North America that the treatment, called TheraSphere, reduced the tumor size by more than 50% in 25% of patients. All of the 19 patients who received TheraSphere treatment as outpatients had been previously treated with CPT-11, said Kennedy, who is a radiation oncologist at the University of Maryland Greenebaum Cancer Center in Baltimore. The FDA gave approval to the TheraSphere treatment in March 2001.

Hepatic Arterial Infusion

Another therapy, hepatic arterial infusion, delivers chemotherapeutic agents directly into the hepatic artery via a pump that has been surgically implanted in the abdomen. An ongoing study at Memorial Sloan-Kettering Cancer Center, New York, has shown that patients with liver metastases from colorectal cancer benefit from combined therapy consisting of hepatic arterial infusion of chemotherapy and systemic chemotherapy.

A 1999 report on these patients showed that 86% of the patients receiving combined therapy survived 2 years, which was statistically significantly greater than those in the control group, whose 2-year survival rate was 72%. Patients were randomly assigned to a combined therapy group or to a systemic chemotherapy-only group.

Updating information about on patients, Nancy Kemeny, M.D., an oncologist in the Department of Medicine at Sloan-Kettering, said recently that about 60% of the group of patients who received combined therapy and about 45% of those patients getting monotherapy were alive at 5 years. During the same time frame, about 70% of the patients who received the combined treatment and about 45% who received only systemic treatment have had no recurrence in the liver.

"We are really protecting the liver from further recurrence," said Kemeny.

"We have also begun using hepatic arterial therapy and systemic therapy after cryosurgery or radiofrequency ablation, with excellent results," Kemeny added. "Future studies will have to be done to compare these modalities with surgery."



             
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