Vandetanib (ZD6474), a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinases: Current Status and Future Directions

被引：169

作者：

Morabito, Alessandro ^{[1
]}

Piccirillo, Maria Carmela ^{[1
]}

Falasconi, Fabiano ^{[1
]}

De Feo, Gianfranco ^{[1
]}

Del Giudice, Antonia ^{[1
]}

Bryce, Jane ^{[1
]}

Di Maio, Massimo ^{[1
]}

De Maio, Ermelinda ^{[1
]}

Normanno, Nicola ^{[2
]}

Perrone, Francesco ^{[1
]}

机构：

[1] Natl Canc Inst, Clin Trials Unit, I-80131 Naples, Italy

[2] CROM, Mercogliano, AV, Italy

来源：

ONCOLOGIST | 2009年 / 14卷 / 04期

关键词：

Vandetanib; VEGFR; EGFR; RET; Clinical trials; RANDOMIZED PHASE-II; ANTITUMOR-ACTIVITY; ACQUIRED-RESISTANCE; ADDITIONAL ACTIVITY; JAPANESE PATIENTS; CANCER-CELLS; LUNG-CANCER; KDR VEGFR-2; OPEN-LABEL; ANGIOGENESIS;

D O I：

10.1634/theoncologist.2008-0261

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses <= 300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a pre-planned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib. The Oncologist 2009; 14: 378-390

引用

页码：378 / 390

页数：13

共 60 条

[1] Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) [J].