5-Fluorouracil and <i>d, </i><i>l</i>-Leucovorin Calcium Are Active to Treat Unresectable Hepatocellular Carcinoma Patients: Preliminary Results of a Phase II Study

Abstract

Twenty-five patients affected with unresectable hepatocellular carcinomas (HCCs) were treated with 370 mg/m² 5-fluorouracil (5-FU) plus 200 mg/m² racemic leucovorin both for 5 consecutive days. The chemotherapy cycle was repeated every 4 weeks until disease progression. One complete remission (4%) and 6 partial responses (24%) were obtained, that is 7 objective responses in all (28%, ninety-five confidence interval: 10.1–45.9%). All responders had a good PS and only 1 of them presented with bulky disease. Five patients (20%) exhibited stable disease, while the remaining 13 patients (52%) progressed. Toxicity was mild: 11 patients (44%) had grade II/III mucositis, 10 patients (40%) grade II diarrhea, 7 patients (28%) grade II nausea, 2 patients grade III granulocytopenia and 1 patient only (4%) grade I skin toxicity. This regimen made it possible to obtain a high rate of objective responses even in inoperable HCCs which are commonly considered as chemoresistant lesions.

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…A phase II study of 5-FU combined with leucovorin showed modest activity with 28% response rates in advanced HCC (13). However, another phase II study of 5-FU with leucovorin showed poor clinical response with only 1 partial response (7%) (14).…”

Chemotherapy with etoposide, doxorubicin, cisplatin, 5-fluorouracil, and leucovorin for patients with advanced hepatocellular carcinoma

“…Therefore, combination therapy is considered to be more effective than monotherapy. There have been various combination chemotherapy in treating advanced HCC [8,9,11,12,22,23] or other malignancies [24]. Combination of etoposide, doxorubicin, cisplatin, Fig.…”

“…Various schedules and dose intensities of 5-FU (F) have been studied [4][5][6]. Biochemical modulation of 5-FU by leucovorin (L) has been found to enhance 5-FU-induced cytotoxicity and clinical effects [7][8][9]. Cisplatin and 5-FU (PF) are synergistic in vitro [10], and PF chemotherapy has resulted in a favorable response in advanced HCC [11,12].…”

Medical Management Options for Hepatocellular Carcinoma

“…Response rates w i t h 5 -F U m o n o t h e r a p y h a v e b e e n l o w . H o w e v e r , w h e n g i v e n i n c o m b i n a t i o n w i t h leucovorin, response rates as high as 28 percent have been reported (Porta et al, 1995).…”