INTRAARTERIAL HEPATIC CHEMOTHERAPY WITH 5-FLUOROURACIL AND 5-METHYLTETRAHYDROFOLATE IN THE TREATMENT OF UNRESECTABLE LIVER METASTASES FROM COLORECTAL-CANCER

Treatment of patients with hepatic metastases from colorectal cancel u sing hepatic artery fluorodeoxyuridine (FUDR) has been reported to ind uce high remission rates but also a high incidence of limiting hepatob iliary toxicity. In an attempt to obviate the limiting FUDR toxic effe cts a phase I-II study was undertaken to establish the efficacy and to lerability of intra-hepatic 5-fluorouracil (5-FU) when given in combin ation with 5-methyltetrahydrofolate. Patients with colorectal liver me tastases (n=17) received escalating doses of 5-FU as a 1 h infusion wi th a fixed dose (100 mg/m(2)) of intra-hepatic 5-methyltetrahydrofolat e (4 h infusion) once a week. Dose limiting toxicity was hepatic and g astrointestinal (diarrhea) and occurred at doses greater than or equal to 350 mg/m(2) 5-FU. Other adverse effects included nausea/vomiting a nd cutaneous toxicity. One patient achieved a complete response and 2 a partial response (mean duration= 9 months) while II had stable disea se. Patients with complete or partial responses had a mean survival of 17 months, while patients with stable disease survived 13 months and those with disease progression 5.5 months on average. These results su ggest that this is a well tolerated regimen although with efficacy at the lower level of the range observed with fluoropyrimidines.