Chiun Hsu1, Tsai-Sheng Yang2, Teh-Ia Huo3, Ruey-Kuen Hsieh4, Chih-Wei Yu5, Wei-Shou Hwang6, Tsai-Yuan Hsieh7, Wen-Tsung Huang8, Yee Chao9, Robin Meng10, Ann-Lii Cheng11. 1. Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 2. Division of Hematology and Oncology, Chang-Gung Memorial Hospital Linkou, Linkou, Taiwan. 3. Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan. 4. Division of Hematology and Oncology, Mackay Memorial Hospital, Taipei, Taiwan. 5. Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan. 6. Division of Hematology and Oncology, Chie-Mei Medical Center Yong-Kang Branch, Tainan, Taiwan. 7. Division of Gastroenterology, Tri-Service General Hospital, Taipei, Taiwan. 8. Division of Hematology and Oncology, Chie-Mei Medical Center Liouying Branch, Tainan, Taiwan. 9. Cancer Treatment Center, Taipei Veterans General Hospital, Taiwan. 10. AstraZeneca, Taipei, Taiwan. 11. Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
Abstract
BACKGROUND & AIMS: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. METHODS: Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. CONCLUSIONS: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies. Copyright Â
BACKGROUND & AIMS: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. METHODS: Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. CONCLUSIONS: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies. Copyright Â
Authors: Hyunki Kim; Kimberly S Keene; David B Sarver; S Kyle Lee; T Mark Beasley; Desiree E Morgan; James A Posey Journal: Gastrointest Cancer Res Date: 2014-05