A randomized, double-blind, phase IIa dose-finding study of vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer

Katsuyuki Kiura, Kazuhiko Nakagawa, Tetsu Shinkai, Kenji Eguchi, Yuichiro Ohe, Nobuyuki Yamamoto, Masahiro Tsuboi, Soichiro Yokota, Takashi Seto, Haiyi Jiang, Kazuto Nishio, Nagahiro Saijo, Masahiro Fukuoka

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Abstract

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

Original languageEnglish
Pages (from-to)386-393
Number of pages8
JournalJournal of Thoracic Oncology
Volume3
Issue number4
DOIs
Publication statusPublished - Apr 2008

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Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Mutation
Vascular Endothelial Growth Factor Receptor
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Exanthema
DNA Sequence Analysis
Vascular Endothelial Growth Factor A
Exons
Diarrhea
Japan
Hypertension
Safety
Drug Therapy
Pharmaceutical Preparations

Keywords

  • EGFR
  • Non-small cell lung cancer
  • Vandetanib
  • VEGFR

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

A randomized, double-blind, phase IIa dose-finding study of vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer. / Kiura, Katsuyuki; Nakagawa, Kazuhiko; Shinkai, Tetsu; Eguchi, Kenji; Ohe, Yuichiro; Yamamoto, Nobuyuki; Tsuboi, Masahiro; Yokota, Soichiro; Seto, Takashi; Jiang, Haiyi; Nishio, Kazuto; Saijo, Nagahiro; Fukuoka, Masahiro.

In: Journal of Thoracic Oncology, Vol. 3, No. 4, 04.2008, p. 386-393.

Research output: Contribution to journalArticle

Kiura, K, Nakagawa, K, Shinkai, T, Eguchi, K, Ohe, Y, Yamamoto, N, Tsuboi, M, Yokota, S, Seto, T, Jiang, H, Nishio, K, Saijo, N & Fukuoka, M 2008, 'A randomized, double-blind, phase IIa dose-finding study of vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer', Journal of Thoracic Oncology, vol. 3, no. 4, pp. 386-393. https://doi.org/10.1097/JTO.0b013e318168d228
Kiura, Katsuyuki ; Nakagawa, Kazuhiko ; Shinkai, Tetsu ; Eguchi, Kenji ; Ohe, Yuichiro ; Yamamoto, Nobuyuki ; Tsuboi, Masahiro ; Yokota, Soichiro ; Seto, Takashi ; Jiang, Haiyi ; Nishio, Kazuto ; Saijo, Nagahiro ; Fukuoka, Masahiro. / A randomized, double-blind, phase IIa dose-finding study of vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer. In: Journal of Thoracic Oncology. 2008 ; Vol. 3, No. 4. pp. 386-393.
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abstract = "INTRODUCTION: Vandetanib (ZACTIMA) is a once-daily, oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling. Vandetanib was evaluated as a monotherapy in a randomized, double-blind, dose-finding study in Japan. PATIENTS AND METHODS: Eligible patients with locally advanced or metastatic (stage IIIB/IV) or recurrent non-small cell lung cancer, previously treated with chemotherapy, were randomized to receive once-daily oral vandetanib 100, 200, or 300 mg (1:1:1). The primary objective was to determine the objective response rate for each vandetanib dose. RESULTS: Fifty-three patients received vandetanib (100 mg, n = 17; 200 mg, n = 18; 300 mg, n = 18). The objective response rate in each dose arm was 17.6{\%} (3 of 17; 100 mg), 5.6{\%} (1 of 18; 200 mg), and 16.7{\%} (3 of 18; 300 mg). Common adverse events included rash, diarrhea, hypertension, and asymptomatic QTc prolongation. The adverse event profile was generally consistent with that reported previously for agents that inhibit the VEGFR or EGFR signaling pathways. Among the three responders evaluated for EGFR mutation, two had no mutation, and in one case, the EGFR mutation status could not be determined by direct DNA sequencing and amplification refractory mutation system assay of EGFR exons 19-21. Baseline plasma VEGF levels appeared to be lower in patients who experienced clinical benefit after vandetanib treatment. CONCLUSION: In Japanese patients with advanced non-small cell lung cancer, vandetanib monotherapy (100-300 mg/d) demonstrated antitumor activity with an acceptable safety and tolerability profile.",
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AU - Eguchi, Kenji

AU - Ohe, Yuichiro

AU - Yamamoto, Nobuyuki

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AU - Yokota, Soichiro

AU - Seto, Takashi

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