BALTIMOREBetween 11,000 and 12,000 colorectal cancer patients present with liver metastases each year. Surgical resection is ideal but does not remove microscopic metastases and disease left behind after surgery. "Today, treatment should start with neoadjuvant therapy in all colorectal cancer patients that have liver metastases," Yehuda Z. Patt, MD, said.
The main approaches to colorectal cancer liver metastases include regional chemotherapy via hepatic arterial infusion (HAI), systemic chemotherapy, or combined modality therapy. Dr. Patt, who is chief of ambulatory care and of gastrointestinal oncology at the University of Maryland Greenebaum Cancer Center in Baltimore, said that little survival advantage has been seen in trials of HAI.
"HAI was an attempt to extract an extra mile from a marginally active drug floxuridine (FUdR) by increasing tumor drug exposure and improving specificity. Despite improved response rates, survival advantage has been equivocal, and administering floxuridine in this fashion was associated with significant biliary toxicity. Newer agents may accomplish improved tumor specificity without HAI."
Attempts to use monoclonal antibodies as drug carriers to increase specificity have been disappointing, but Dr. Patt said, "Use of enzymatic properties unique to the tumor, as with capecitabine(Drug information on capecitabine) (Xeloda), may provide the improved specificity we are looking for."
Resect When Possible
Dr. Patt outlined a suggested approach to metachronous liver metastases beginning with systemic fluoropyrimidine plus irinotecan(Drug information on irinotecan) (CPT-11, Camptosar) or oxaliplatin(Drug information on oxaliplatin) (Eloxatin) or all three agents. "Whenever possible we should then resect the responding metastases. Postoperatively, we should treat the patient with the regimen that produced the response and reserve HAI for liver metastases that do not respond," Dr. Patt said. "If the lesions respond to HAI, we should resect and give postoperative HAI as adjuvant treatment."
Current recommendations for patients with rectal cancer and resectable synchronous liver metastases are resection of the liver metastases and primary tumor with postoperative adjuvant fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin or adjuvant radiation/5-FU plus two cycles of 5-FU/leucovorin. The current recommendations for rectal cancer with nonresectable liver metastases, include segmental rectal resection or laser ablation, diverting colostomy or radiotherapy/5-FU, and salvage chemoradiotherapy. However, Dr. Patt suggested "the use of neo-adjuvant therapy in nearly all patients."