Hepatic transcatheter arterial chemoembolization alternating with systemicprotracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: A phase II trial of the Puget sound oncology consortium (PSOC 1104)

We assessed a regimen of alternating regional and systemic therapy in patie nts,vith gastrointestinal malignancies with liver-dominant metastases for f easibility, toxicity, response rate, response duration, patterns of progres sion, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure w as delivered between cycles of protracted continuous infusion 5-fluorouraci l (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included : (a) having histologically documented adenocarcinoma arising from a gastro intestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod), PCI-5FU (250 mg/m(2)/day) was admi nistered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe,vith the greatest tumor burden. Rest aging was performed before TACE 2 and TACE 3, which followed at monthly int ervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatme nts. After the final TACE, maintenance PCI-5FU was given for 28 days of eac h 35-day cycle until toxicity or progression. Between December 23, 1991, an d January 19, 1995, 32 patients were registered in this trial, of whom 27 w ere eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predom inated (74%), Twelve (44%) of 27 patients had failed one or more prior trea tment regimens. There were no treatment-related deaths, and hematological a nd hepatic toxicities were generally manageable and reversible. Two patient s, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy, Th ere were no patients with complete responses; there were 8 (40%) with parti al responses, 4 (20%) with minor responses, 2 (10%) with stable disease, an d 6 (30%) who progressed on the treatment. The median duration of response for partial responders was 4.2 months (127 days; range, 56-245 days), The m edian reduction in carcinoembryonic antigen for responders was 87.5%. Two p atients underwent subsequent resection of residual metastases; one of them is still alive at 58.4 months follow-up, The predominant site of disease pr ogression was the liver; 25% of the patients progressed in extrahepatic sit es. The median overall survival for the whole group is 14.3 months (95% con fidence interval, 7.2-16.2). Actuarial overall survival for the whole group at 1 year and 2 years is 57 and 19%, respectively. Alternating systemic PC I-5FU and regional TACE (cisplatin/polyvinyl alcohol) is an active and feas ible regimen with manageable toxicities in patients with metastatic gastroi ntestinal malignancies with liver dominant disease and merits further inves tigation. The complications seen were in line with those reported at other specialized centers.