5-fluorouracil plus high dose levofolinic acid and oral hydroxyurea for the treatment of primary hepatocellular carcinomas: Results of a phase II multicenter study of the southern Italy Oncology Group (GOIM)

A phase II trial of 5FU in modulation with intravanous high-dose levofolini c acid and oral hydroxyurea (HU) in advanced unresectable hepatocellular ca rcinoma (HCC). A total of 50 consecutive patients, 38 males (76%) and 12 fe males (24%), with a mean age of 62 years (mange 30-74) and a mean performan ce status of 80 (KI, range 60-90) were enrolled The vast majority of patien ts were therapy-naive, although two patients (4%) had previous surgery and showed progressive disease at Entry. No patient had been previously treated with chemotherapy. Five patients had previous hormonotherapy with tamoxife n. Most patients had disease limited to the liver while 12 patients (24%) h ad also metastatic deposits outside the liver. The treatment plan included levofolinic acid 100 mg/m(2) diluted in 500 cc of normal saline over 2 hour infusion followed by 5FU 600 mg/m(2) i.v. bolus. HU 1,000 mg/m(2) was give n by mouth in three refracted doses starting 6 hours after 5FU. A PR was re corded in only 5 patients (10%; 95% CL 1% - 34%) with a median duration of 5.7+ months (range 4.0 / 6.2 months), a stabilization in 15 (30%) with a me dian duration of 3.8 months, while 30 patients progressed (60%). PR were se en at liver primary tumor in 4 cases and at soft tissue in I case. The medi an survival was 5.8 months (range 2.0 / 12.0+). The most frequent toxicitie s were leukopenia (32%), which however was mild (grade 1-2) in all casesl a nd grade 1-2 thrombocytopenia observed in 15% of cases. Mild grade 1-2 vomi ting was recorded in one third of patients, and grade 1-2 stomatitis in 15% . The combination of 5FU with levofolinic acid and oral HU on a weekly shed ule is largely inactive against unresectable or metastatic HCC and results are no better than historical data reported for 5FU alone.