Journal of Clinical Oncology, Vol 15, 1432-1438, Copyright © 1997 by American Society of Clinical Oncology
Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin
YZ Patt, A Hoque, R Lozano, R Pozdur, J Chase, H Carrasco, V Chuang, ES Delpassand, L Ellis, S Curley, M Roh and DV Jones Jr
Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030-4095, USA.
PURPOSE: To determine the toxicity, response rate, and survival in patients
treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus
recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A;
Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver
metastases refractory to systemic 5-FU plus leucovorin (LCV). PATIENTS AND
METHODS: Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5
MU/m2 followed by an 18-hour HAI of 5- FU, 1,500 mg/m2 daily for 5 days.
Twenty-nine patients were treated through percutaneously placed catheters
and 19 through implantable infusion pumps (Shiley Infusaid Inc, Noorwood,
MA). Treatment cycles were repeated every 28 to 35 days. RESULTS: There
were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial
remissions (PRs), for a CR plus PR rate of 33.3% among 45 assessable
patients (95% confidence interval [CI], 20% to 49%). The median response
duration was 7 months, while median survival duration was 15 months. Grade
3 to 4 treatment- related toxic effects included mucositis (40%),
neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity
was encountered in any of the patients. Treatment was discontinued because
of progressive liver disease in 23 patients and extrahepatic progression in
16, while six patients continue treatment through an infusaid pump.
CONCLUSION: HAI of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of
hepatobiliary toxicity, and can produce a response rate of 33.3% among
patients refractory to bolus intravenous (IV) 5-FU plus LCV. The lack of
hepatobiliary toxicity may permit salvage HAI with floxuridine (FUDR) in
patients whose liver tumors fail to respond to HAI of 5-FU plus rIFN-alpha
2b. Because diarrhea was not a common side effect of HAI of 5-FU plus
rIFN-alpha 2b, it would be of interest to investigate whether alternating
HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will
decrease the incidence of both hepatic and extrahepatic disease
progression.
