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Investigational New Drugs

, Volume 22, Issue 1, pp 69–73 | Cite as

A Phase II Study of 9-Nitro-Camptothecin in Patients with Previously Treated Metastatic Breast Cancer

  • Kathy D. Miller
  • Sharon E. Soule
  • LaTrice G. Haney
  • Patricia Guiney
  • Darryl J. Murry
  • Luigi Lenaz
  • Show-Li Sun
  • George W. SledgeJr
Article

Abstract

Aims: This Phase II study was conducted to determine the efficacy and toxicity of 9-nitro-camptothecin (9-NC) in patients with previously treated metastatic breast cancer. Pharmacokinetic samples were obtained to investigate the correlation of plasma 9-NC exposure with clinical response and toxicity. Patients and methods: Eligible patients had histologically confirmed metastatic breast cancer with measurable or evaluable disease. Patients must have received one or two prior chemotherapy regimens for metastatic disease. 9-NC was given orally, 1.5 mg/m2/day for 5 days each week; response was assessed every 8 weeks. Pharmacokinetic samples were obtained on day 1 of weeks 1 and 5. Results: Eighteen patients were enrolled between September 1999 and May 2000; seventeen patients were evaluable for response. The most common toxicities were nausea, vomiting, urinary symptoms, fatigue and diarrhea. No objective responses were observed; six patients had stable disease. 9-NC apparent clearance ranged from 0.57 to 55.08 L/h (median 5.91 L/h); 9-NC area under the curve ranged from 38 to 2130 ng/ml×h (median 377 ng/ml×h). There was no relationship between pharmacokinetic parameters and individual patient toxicity. Conclusion: 9-NC has limited activity in patients with previously treated metastatic breast cancer. Though 9-NC has substantial pharmacokinetic variability in this patient population; no correlation was found between pharmacokinetic variables and toxicity.

topoisomerase inhibitor chemotherapy clinical trial 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Kathy D. Miller
    • 1
  • Sharon E. Soule
    • 1
  • LaTrice G. Haney
    • 1
  • Patricia Guiney
    • 1
  • Darryl J. Murry
    • 2
  • Luigi Lenaz
    • 3
  • Show-Li Sun
    • 3
  • George W. SledgeJr
    • 1
  1. 1.Division of Hematology and OncologyIndiana UniversityIndianapolis
  2. 2.Department of PharmacologyPurdue UniversityWest Lafayette
  3. 3.Supergen, Inc.San RamonU.S.A

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