PHASE-II TRIAL OF ORAL DOXIFLURIDINE PLUS ORAL LEVO-LEUCOVORIN IN UNRESECTABLE HEPATOCELLULAR-CARCINOMA

: Systemic chemotherapy with currently available agents in unresectable HCC has a minimal impact on disease progression and a predictable response rate of <20%. Doxifluridine (5 deoxy-5-fluorouridine, dFUR) is a new fluropyrimidine derivative that demonstrated higher antitumoral activity than other fluoropyrimidines in murine tumors and optimal gastrointestinal absorption when administered orally. Therefore, we evaluated the activity and feasibility of a combination of dFUR and l-leucovorin in unresectable HCC by the following schedule: l-leucovorin 25 mg orally followed 2 hours later by dFUR 1,200 mg/m(2), day 1 through 5, cycles being repeated every 10 days. Thirtyseven patients with unresectable HCC entered the study and are evaluable for response and toxicity. Three partial responses have been observed, to a global response rate of 8% (95% confidence interval 2-22%). After a median observation time of 12 months, the median survival was 7 months, with a median time to progression of 4 months; Main toxicity was diarrhea; severe in 30% of the patients. One patient died as a result of uncontrollable diarrhea. In view of the limited activity observed, further trials with this schedule are not warranted.