Prevention of extrahepatic disease during intraarterial floxuridine of colorectal liver metastases by simultaneous systemic 5-fluorouracil treatment? A prospective multicenter study.

Fifty-two (52) patients with nonresectable hepatic-only metastases from colorectal carcinoma (tumor volume less than 75%) were treated by intraarterial FUdR, 0.2 mg/kg/d x 14 days/month (IA) using implantable pumps (Infusaid). They were randomized either for IA or for IA + systemic 5-FU 700 mg/m2/d x 3 days/month (IA/IV). Forty-six (46) patients were evaluable (26 IA; 20 IA/IV). Both groups were comparable in respect to primary tumor stage, age, liver function tests, tumor markers and extent of tumor infiltration. Twenty-six (26) patients (56%) demonstrated a complete (CR) or partial response (PR) with at least a 50% decrease in CEA levels and a significant tumor volume reduction (IA 50%; IA/IV 65%). Quality of response was significantly correlated with median survival (MS) time of 25 months for CR and PR. Approximate MS for IA and IA/IV was 16 and 19.5 months, respectively, and approximate median survival time to extra- and/or intrahepatic progression was 9 months (IA) and 11 months (IA/IV). Incidence of extrahepatic recurrence was not influenced by any treatment (IA 62%; IA/IV 60%). Overall approximate median time to occurrence of extrahepatic disease was 12.5 months (IA 13; IA/IV 10). Liver disease progression was observed in 38 patients (IA 85%; IA/IV 80%). A median time of 8 months to diagnosis of liver disease progression was calculated for IA, and IA/IV was 11.5 months. Incidence of chemical hepatitis for IA and IA/IV was 54 and 45%, while biliary sclerosis occurred in 15% and 10% of the cases, respectively, and did not correlate with response rates. Systemic side effects (25%) were only observed in the IA/IV group and induced significantly more interruptions of therapy than in the IA group. It is concluded from this study that additional systemic 5-FU treatment does not prevent the occurrence of extrahepatic disease under local chemotherapy of the liver.