Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma
Journal
Journal of Hepatology
Journal Volume
53
Journal Issue
1
Pages
126-131
Date Issued
2010
Author(s)
Abstract
Background & Aims: Sorafenib, a multi-kinase inhibitor with anti-angiogenic activity, was recently approved for the treatment of advanced hepatocellular carcinoma (HCC). Metronomic chemotherapy using tegafur/uracil (4:1 molar ratio), an oral fluoropyrimidine, has been shown to enhance the anti-tumor effect of anti-angiogenic agents in preclinical models. This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC. Methods: Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib (400 mg twice daily) and tegafur/uracil (125 mg/m2 based on tegafur twice daily) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies. The primary endpoint was progression-free survival (PFS). Results: The study enrolled 53 patients. Thirty-eight patients (72%) were hepatitis B surface antigen-positive. The median PFS was 3.7 months (95% C.I., 1.9-5.5) and the median overall survival was 7.4 months (95% C.I., 3.4-11.4). According to RECIST criteria, 4 patients (8%) had a partial response and 26 patients (49%) had a stable disease. Major grade 3/4 toxicities included fatigue (15%), abnormal liver function (13%), elevated serum lipase (10%) hand-foot skin reaction (HFSR) (9%), and bleeding (8%). HFSR was the major adverse event resulting in dose reduction (19%) or treatment delay (21%). Conclusions: Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients. ? 2010 European Association for the Study of the Liver.
SDGs
Other Subjects
alpha fetoprotein; aminotransferase; creatinine; hepatitis B surface antigen; sorafenib; triacylglycerol lipase; UFT; ufur; unclassified drug; antineoplastic agent; benzenesulfonic acid derivative; carbanilamide derivative; nicotinamide; protein kinase inhibitor; pyridine derivative; sorafenib; tegafur; uracil; adult; advanced cancer; age distribution; aged; anemia; anorexia; article; bleeding; cancer chemotherapy; cancer survival; clinical trial; cytology; diarrhea; disease classification; drug dose reduction; drug efficacy; drug safety; drug withdrawal; edema; epigastric pain; esophagus varices; fatigue; female; fever; gastric ulcer bleeding; hair loss; hand foot syndrome; hoarseness; human; hyperbilirubinemia; hypermagnesemia; hypertension; hypocalcemia; hyponatremia; infection; leukopenia; liver cell carcinoma; liver function; liver histology; liver metastasis; major clinical study; malaise; male; metronomic chemotherapy; mucosa inflammation; nausea; neutropenia; open study; outcome assessment; overall survival; phase 2 clinical trial; priority journal; prognosis; progression free survival; protein blood level; proteinuria; scoring system; sex difference; side effect; taste disorder; therapy delay; thrombocytopenia; treatment response; triacylglycerol lipase blood level; vomiting; analogs and derivatives; anorexia; Carcinoma, Hepatocellular; chemically induced; diarrhea; disease free survival; Drug Eruptions; fatigue; Kaplan Meier method; Liver Neoplasms; middle aged; very elderly; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Carcinoma, Hepatocellular; Diarrhea; Disease-Free Survival; Drug Eruptions; Fatigue; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Pyridines; Tegafur; Uracil
Publisher
Elsevier
Type
journal article