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 resp onse rate of <20%. Doxifluridine (5 deoxy-5-fluorouridine, dFUR) is a new fluropyrimidine derivative that demonstrated higher antitumoral ac tivity than other fluoropyrimidines in murine tumors and optimal gastr ointestinal absorption when administered orally. Therefore, we evaluat ed the activity and feasibility of a combination of dFUR and l-leucovo rin 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 unresec table HCC entered the study and are evaluable for response and toxicit y. Three partial responses have been observed, to a global response ra te of 8% (95% confidence interval 2-22%). After a median observation t ime 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 diarr hea. In view of the limited activity observed, further trials with thi s schedule are not warranted.