Efficacy, safety, and potential biomarkers of thalidomide plus metronomic chemotherapy for advanced hepatocellular carcinoma
Journal
Oncology
Journal Volume
82
Journal Issue
1
Pages
59-66
Date Issued
2012
Author(s)
Lee, Kuan-Der
Hsiao, Chi-Huang
Huang, Chien-Chung
Abstract
Objectives: Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy. Methods: This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment-na?ve advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m2 (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes. Results: Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7-2.1 months), and the median OS was 4.6 months (95% CI 2.3-6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals. Conclusions: The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC. Copyright ? 2012 S. Karger AG, Basel.
SDGs
Other Subjects
angiogenic factor; interleukin 6; interleukin 8; pharmacological biomarker; thalidomide; tumor necrosis factor alpha; UFT; ufur; unclassified drug; vasculotropin A; abdominal distension; adult; advanced cancer; aged; aminotransferase blood level; anemia; anorexia; article; clinical article; clinical assessment; constipation; controlled study; correlation analysis; diarrhea; dizziness; drug dose escalation; drug dose reduction; drug efficacy; drug safety; drug withdrawal; edema; female; gastrointestinal hemorrhage; hand foot syndrome; hepatitis B; human; hyperbilirubinemia; hyponatremia; leukopenia; liver cell carcinoma; malaise; male; metronomic drug administration; mucosa inflammation; multicenter study; neutropenia; outcome assessment; overall survival; paresthesia; patient compliance; peripheral neuropathy; phase 2 clinical trial; priority journal; progression free survival; protein blood level; pruritus; rash; side effect; somnolence; thrombocytopenia; vomiting; xerostomia; Administration, Oral; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Disease Progression; Disease-Free Survival; Female; Hepatitis B virus; Humans; Interleukin-6; Interleukin-8; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Thalidomide; Treatment Outcome; Tumor Markers, Biological
Type
journal article