Colorectal cancer patients whose cancer had spread to their livers benefited from surgery during which heated chemotherapy was pumped directly to their livers. Isolated hepatic perfusion (IHP) shrank tumors and increased survival time. It may be a hopeful new approach to treating colorectal cancer that is widespread in the liver.
Median survival time after the treatment was a little over 17 months. A third of patients lived two years or more.
A clinical trial of a similar hepatic perfusion technique without open surgery is currently available at the NIH Clinical Center in Bethesda, Maryland.
During an abdominal operation, surgeons placed tubes in major blood vessels in the liver. Heated chemotherapy was then pumped for about sixty minutes through the liver. This technique allows stronger chemo to be delivered directly liver tissue and avoids the side effects of chemotherapy that goes throughout the body.
Two drugs were used in the reported studies: melphalan and tumor necrosis factor (TNF). Some patients received only melphalan, some only TNF, and some both. In addition, some patients had a pump placed in their abdomen to infuse chemotherapy into their liver through the hepatic artery after the surgical treatment.
There were 120 patients who had some form of hepatic perfusion treatment, 114 available to be evaluated for this report.
- 69 patients had either complete (2) or partial (67) tumor shrinkage (61 percent)
- Median time until cancer recurred in the liver was 7 months
- There was no clinically meaningful tumor reduction in the 10 patients who received TNF alone
- Median time to cancer progression in the liver for TNF alone group was 3 months.
- Patients who didn’t receive additional hepatic arterial infusion (HAI) after surgery had 57 percent response and a median time to liver progression of 5.8 months.
- HAI improved both response rate to 65 percent and time to liver progression to 13 months.
Response rate was not affected by the amount of tumor in the liver, by previous chemotherapy, age, or gender.
Serious side effects of treatment included changes in liver function tests after surgery that returned to normal, very low blood pressure in some patients, bleeding, and infection. Five patients died, although these deaths occurred in early phase I trials of TNF when finding a tolerable dose was the goal.
In reflecting on the results of their studies, researchers at the University of Maryland Medical School in Baltimore and the National Cancer Institute in Bethesda led by H. Richard Alexander, Jr. M.D. wrote,
Regional therapy eliminates unnecessary systemic toxicity and when used as second-line therapy can be used selectively for those who may benefit most, that is, those with disease that has remained confined to liver by serial imaging over time.
Isolated hepatic perfusion results in marked tumor regression and prolonged survival in patients with colorectal cancer liver metatases. Continued development of IHP in this clinical setting is warranted.
SOURCE: Alexander et al., Annals of Surgical Oncology, Volume 16, Number 7, July 2009.