Cancer Chemotherapy and Pharmacology

, Volume 64, Issue 6, pp 1165–1172 | Cite as

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

  • Noboru Yamamoto
  • Tomohide Tamura
  • Nobuyuki Yamamoto
  • Kazuhiko Yamada
  • Yasuhide Yamada
  • Hiroshi Nokihara
  • Yutaka Fujiwara
  • Toshiaki Takahashi
  • Haruyasu Murakami
  • Narikazu Boku
  • Kentaro Yamazaki
  • Thomas A. Puchalski
  • Eisei Shin
Original Article

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.

Keywords

AZD2171 Cediranib Phase I study Tolerability Vascular endothelial growth factor receptor 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Noboru Yamamoto
    • 1
  • Tomohide Tamura
    • 1
  • Nobuyuki Yamamoto
    • 2
  • Kazuhiko Yamada
    • 1
  • Yasuhide Yamada
    • 1
  • Hiroshi Nokihara
    • 1
  • Yutaka Fujiwara
    • 1
  • Toshiaki Takahashi
    • 2
  • Haruyasu Murakami
    • 2
  • Narikazu Boku
    • 2
  • Kentaro Yamazaki
    • 2
  • Thomas A. Puchalski
    • 3
    • 5
  • Eisei Shin
    • 4
  1. 1.Division of Internal MedicineNational Cancer Center HospitalTokyoJapan
  2. 2.Division of Thoracic OncologyShizuoka Cancer Center HospitalShizuokaJapan
  3. 3.AstraZenecaWilmingtonUSA
  4. 4.AstraZeneca KKOsakaJapan
  5. 5.CentocorChesterbrookUSA

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