A Randomized, Double-Blind, Phase IIa Dose-Finding Study of Vandetanib (ZD6474) in Japanese Patients With Non-Small Cell Lung Cancer

摘要: Introduction Vandetanib (ZACTIMA TM ) is a once-daily, oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor (VEGFR) and epidermal (EGFR) signaling. was evaluated as monotherapy in randomized, double-blind, dose-finding study Japan. Patients Methods Eligible patients with locally advanced or metastatic (stage IIIB/IV) recurrent non-small cell lung cancer, previously treated chemotherapy, were randomized to receive once-daily vandetanib 100, 200, 300 mg (1:1:1). The primary objective determine the response rate for each dose. Results Fifty-three received (100 mg, n = 17; 200 18; 18). dose arm 17.6% (3 of 100 mg), 5.6% (1 16.7% mg). Common adverse events included rash, diarrhea, hypertension, asymptomatic QTc prolongation. event profile generally consistent reported agents inhibit VEGFR EGFR signaling pathways. Among three responders mutation, two had no one case, mutation status could not be determined by direct DNA sequencing amplification refractory system assay exons 19–21. Baseline plasma VEGF levels appeared lower who experienced clinical benefit after treatment. Conclusion In Japanese (100–300 mg/d) demonstrated antitumor activity an acceptable safety tolerability profile.