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Upfront Neoadjuvant Therapy Urged for All Colorectal Cancer Patients With Liver Metastases

Upfront Neoadjuvant Therapy Urged for All Colorectal Cancer Patients With Liver Metastases

BALTIMORE—Between 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 (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 (CPT-11, Camptosar) or
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 (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."

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