Hepatic Infusion for Liver Mets: ‘Historic Results’

ASCO—For colorectal cancer patients who have undergone surgery for liver metastases, adjuvant therapy that combines hepatic arterial chemotherapy and systemic chemotherapy effectively controls local disease and significantly increases 2-year survival, Nancy Kemeny, MD, of Memorial Sloan-Kettering Cancer Center, reported at ASCO.

Discussant Nicholas Petrelli, MD, of Roswell Park Cancer Institute, called the results historic. He stopped short, however, of saying that the results should change the standard of care for liver metastases patients, which has been surgery alone. “I think there is cautious optimism,” he said. The therapy, he emphasized, needs to be tested in the prospective randomized cooperative group setting.

The single-institution study included 156 patients randomized after complete resection. One month after surgery, all patients received fluorouracil (5-FU)/leucovorin. In the hepatic arterial group, this was followed, 2 weeks later, by 2 weeks of hepatic arterial infusion of floxuridine and dexamethasone via an implantable pump. After a 1-week rest, the cycle began again—every 5 weeks in the infusion group; every 4 weeks in the systemic group—for six cycles.

The combined modality adjuvant therapy increased 2-year survival (85% vs 69% for systemic chemotherapy alone); increased 2-year hepatic disease-free survival (89% vs 57%); and trended toward an increase in overall survival (57% vs 41%). At a median follow-up of 56 months, median survival has not been reached for the hepatic arterial plus systemic group, Dr. Kemeny said, and is 49 months for the systemic alone group. Actuarial 5-year survival is 60% for the combined modality group and 40% for the systemic only group.

The median overall disease-free survival is 31.3 months for the hepatic artery/systemic arm and 17 months for systemic therapy alone, “indicating that the systemic chemotherapy we used did not adequately control extrahepatic disease,” Dr. Kemeny said. She noted that future studies of the combined modality should explore alternate systemic agents such as irinotecan (Camptosar), which is being used in an ongoing study.

The toxicity was similar in the two groups, except for diarrhea, which was increased in the hepatic arterial arm.

A multi-institution study, presented by Margaret Kemeny, MD, of the State University of New York, Stony Brook, also showed an advantage for hepatic arterial infusion. In this trial, patients undergoing hepatic resection were randomized after surgery to observation or four courses of hepatic arterial infusion of floxuridine and 1 year of systemic 5-FU.

With a median follow-up of 4 years, 3-year recurrence-free survival is 34% for observation vs 58% for combined modality adjuvant therapy (P = .035). Of those patients who recurred, those in the no chemotherapy arm were more likely to have recurrence in the liver than those in the chemotherapy arm (73% vs 50%).

The researchers conclude that hepatic artery infusion and systemic therapy after resection can be done safely with no increase in operative morbidity or mortality, and results in a significant decrease in liver recurrences, a significant increase in 5-year disease-free survival, and a trend toward an improved 5-year overall survival rate.