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Investigational New Drugs

, Volume 25, Issue 5, pp 471–477 | Cite as

Phase II study of Triapine® in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161)

  • Jennifer J. Knox
  • Sebastien J. Hotte
  • Christian Kollmannsberger
  • Eric Winquist
  • Bryn Fisher
  • Elizabeth A. Eisenhauer
PHASE II STUDIES

Summary

Triapine® is a novel small molecule ribonucleotide reductase inhibitor that showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents with novel mechanisms remains of interest for patients with incurable RCC. This was a single-arm, multicentre phase II trial where Triapine was given at a schedule of 96 mg/m2 2-h infusion daily × 4 repeated every 2 weeks in patients with recurrent RCC. A median of four cycles of Triapine was administered to 19 eligible patients. One response was seen (7%.) Median time to progression was 3.6 months. Common adverse events (AEs) were grade 1–2, with fatigue in 74%, nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79% and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose reductions/delays due to AEs were common with only 47% of patients receiving > 90% of planned dose intensity. The study closed, at the end of stage 1 as it did not meet the minimal efficacy criteria to proceed. Further evaluation of Triapine at this dose and schedule in patients with advanced kidney cancer is not recommended.

Keywords

Kidney cancer Phase II Ribonucleotide reductase Renal cell Triapine 

Notes

Acknowledgments

This trial was supported by grants from the National Cancer Institute of Canada, the National Cancer Institute Division of Cancer Therapy Evaluation Program (CTEP) and by Vion Therapeutics. The authors thank the following investigators who in addition to the co-authors enrolled patients on this study: Drs K Belanger, K Chi, S Ernst, I Tannock, P Venner and R Wong.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jennifer J. Knox
    • 1
  • Sebastien J. Hotte
    • 2
  • Christian Kollmannsberger
    • 3
  • Eric Winquist
    • 4
  • Bryn Fisher
    • 5
  • Elizabeth A. Eisenhauer
    • 5
  1. 1.Department of Medical OncologyUniversity Health Network-OCI/Princess Margaret HospitalTorontoCanada
  2. 2.Juravinski Cancer Centre at Hamilton Health SciencesHamiltonCanada
  3. 3.British Columbia Cancer Agency- Vancouver Cancer CentreVancouverCanada
  4. 4.London Health Sciences CentreLondonCanada
  5. 5.NCIC Clinical Trials Group, Queen’s UniversityKingstonCanada

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