Investigational New Drugs

, Volume 24, Issue 6, pp 499–508

A Phase I study of the oral antimetabolite, CS-682, administered once daily 5 days per week in patients with refractory solid tumor malignancies

  • Jill Gilbert
  • Michael A. Carducci
  • Sharyn D. Baker
  • Elizabeth C. Dees
  • Ross Donehower
Phase I Studies

Summary

The development of nucleoside analogues has had a major impact on cancer therapy. CS-682 is a novel, orally administered nucleoside analogue with a unique mechanism of action. CS-682 undergoes conversion to the active metabolite, CNDAC, which then leads to the inhibition of DNA polymerase and a novel “DNA self-strand breaking mechanism.” We conducted a Phase I study of CS-682, administered orally five days per week in patients with refractory solid tumor malignancies. Forty-eight patients were enrolled on study. The recommended phase II dose of 30 mg/m2 given orally once daily for 5 days a week for 4 weeks followed by 2 weeks off drug, was well tolerated. The most common dose limiting toxicity was neutropenia, which occurred at the highest dose levels of CS-682. This was correlated with higher CNDAC Cmax and AUC values. No tumor responses were noted in this heavily pretreated population. However, given the ease of administration and tolerability, further investigation of this agent is warranted.

Keywords

Antimetabolite CS-682 Phase I Pharmacokinetic 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Jill Gilbert
    • 1
  • Michael A. Carducci
    • 2
  • Sharyn D. Baker
    • 2
  • Elizabeth C. Dees
    • 3
  • Ross Donehower
    • 2
  1. 1.Stanley S. Scott Cancer CenterLouisiana State University Health Sciences CenterNew Orleans
  2. 2.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore
  3. 3.Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel Hill

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