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Investigational New Drugs

, Volume 31, Issue 4, pp 1008–1015 | Cite as

A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium

  • Srikala S. Sridhar
  • Mary J. Mackenzie
  • Sebastien J. Hotte
  • Som D. Mukherjee
  • Ian F. Tannock
  • Nevin Murray
  • Christian Kollmannsberger
  • Masoom A. Haider
  • Eric X. Chen
  • Robert Halford
  • Lisa Wang
  • S. Percy Ivy
  • Malcolm J. Moore
PHASE II STUDIES

Summary

Background Inhibition of angiogenesis has emerged as an effective therapeutic strategy in metastatic renal cell cancer (mRCC). In this single arm phase 2 study, we evaluated the efficacy and tolerability of cediranib (AZD2171) a potent angiogenesis inhibitor in first line mRCC. Methods Eligible patients who had no prior systemic therapy received cediranib 45 mg orally once daily continuously. The primary endpoint was objective response rate (ORR). Secondary endpoints were clinical benefit rate (ORR plus stable disease (SD) ≥ 4 months), duration of response, progression free survival (PFS), median overall survival (OS), safety and tolerability. Results Between January 2006 and April 2008, 44 patients were accrued. The median age was 62 (range 44–83) and performance status was either 0 (22 patients) or 1 (22 patients). Of the 39 evaluable patients there were 15 (38 %) partial responses (95 % CI: 23–55 %); 18 stable disease (SD) for a clinical benefit rate of 33/39 = 85 % (95 % CI: 69–94 %) and 6 progressive disease. Median PFS was 8.9 months (95 % CI: 5.1–12.9); and median OS was 28.6 months (95 % CI: 18.2–37.3 months). The most frequent grade 3 or higher AEs included hypertension, fatigue, hand-foot syndrome and diarrhea. Conclusions Cediranib demonstrated significant anti-tumour activity in first line, treatment-naive mRCC, with efficacy parameters comparable to the other approved agents (sunitinib and pazopanib) in this setting. The main toxicities were fatigue, diarrhea and hypertension. Based on these encouraging results, further evaluation of cediranib in mRCC at a more tolerable dose of 30 mg daily appears warranted.

Keywords

Cediranib Advanced renal cell cancer Angiogenesis inhibitor 

Notes

Acknowledgments

This project was supported by an NIH grant. NCI Contracts N01CM17107, N01CM62203

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Srikala S. Sridhar
    • 1
    • 6
  • Mary J. Mackenzie
    • 2
  • Sebastien J. Hotte
    • 3
  • Som D. Mukherjee
    • 3
  • Ian F. Tannock
    • 1
  • Nevin Murray
    • 4
  • Christian Kollmannsberger
    • 4
  • Masoom A. Haider
    • 1
  • Eric X. Chen
    • 1
  • Robert Halford
    • 1
  • Lisa Wang
    • 1
  • S. Percy Ivy
    • 5
  • Malcolm J. Moore
    • 1
  1. 1.Princess Margaret HospitalTorontoCanada
  2. 2.London Regional Cancer CenterLondonCanada
  3. 3.Juravinski Cancer CenterHamiltonCanada
  4. 4.BC Cancer AgencyVancouverCanada
  5. 5.Cancer Therapy Evaluation ProgramNational Cancer InstituteBethesdaUSA
  6. 6.Princess Margaret HospitalUniversity Health NetworkTorontoCanada

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