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Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN™), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors

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Abstract

Purpose

To evaluate safety and tolerability of cediranib, a highly potent and selective vascular endothelial growth factor signaling inhibitor, in Japanese patients with advanced solid tumors refractory to standard therapies.

Methods

In part A (n = 16), patients received once-daily oral cediranib (10–45 mg) to identify the maximum tolerated dose (MTD). In part B (n = 24), patients with non-small-cell lung cancer or colorectal cancer received multiple daily doses at the MTD.

Results

Cediranib 30 mg/day was considered the MTD since 50% of evaluable patients receiving 45 mg/day experienced dose-limiting toxicities in part A (proteinuria and diarrhea n = 1, proteinuria n = 1, thrombocytopenia n = 1). The most common adverse events were diarrhea (n = 34) and hypertension (n = 32). Pharmacokinetic analysis confirmed cediranib as suitable for once-daily oral dosing. Of 32 evaluable patients, two had partial RECIST responses and 24 had stable disease ≥8 weeks.

Conclusions

Cediranib was generally well tolerated at ≤30 mg/day in these Japanese patients and showed encouraging antitumor activity.

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Acknowledgments

This study, including medical writing support provided by Rebecca Helson of Mudskipper Bioscience, was supported financially by AstraZeneca. RECENTIN™ is a trade mark of the AstraZeneca group of companies. Noboru Yamamoto and Tomohide Tamura have received remuneration from AstraZeneca KK and Eisei Shin has stock ownership.

Author information

Author notes

  1. Thomas A. Puchalski

    Present address: Centocor, Chesterbrook, PA, USA

Authors and Affiliations

  1. Division of Internal Medicine, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan

    Noboru Yamamoto, Tomohide Tamura, Kazuhiko Yamada, Yasuhide Yamada, Hiroshi Nokihara & Yutaka Fujiwara

  2. Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan

    Nobuyuki Yamamoto, Toshiaki Takahashi, Haruyasu Murakami, Narikazu Boku & Kentaro Yamazaki

  3. AstraZeneca, Wilmington, DE, USA

    Thomas A. Puchalski

  4. AstraZeneca KK, Osaka, Japan

    Eisei Shin

Authors
  1. Noboru Yamamoto
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  2. Tomohide Tamura
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  3. Nobuyuki Yamamoto
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  4. Kazuhiko Yamada
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  5. Yasuhide Yamada
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  7. Yutaka Fujiwara
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  10. Narikazu Boku
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  11. Kentaro Yamazaki
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  12. Thomas A. Puchalski
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  13. Eisei Shin
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Corresponding author

Correspondence to Noboru Yamamoto.

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Yamamoto, N., Tamura, T., Yamamoto, N. et al. Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN™), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 64, 1165–1172 (2009). https://doi.org/10.1007/s00280-009-0979-8

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  • DOI: https://doi.org/10.1007/s00280-009-0979-8

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