A Phase II study of 9-nitro-camptothecin in patients with previously treated metastatic breast cancer

Kathy Miller, Sharon E. Soule, LaTrice G. Haney, Patricia Guiney, Darryl J. Murry, Luigi Lenaz, Show Li Sun, George W. Sledge

Research output: Contribution to journalArticle

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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 x h (median 377 ng/ml x 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.

Original languageEnglish
Pages (from-to)69-73
Number of pages5
JournalInvestigational New Drugs
Volume22
Issue number1
DOIs
StatePublished - Jan 2004

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Camptothecin
Breast Neoplasms
Pharmacokinetics
Nausea
Area Under Curve
Vomiting
Fatigue
Diarrhea
Drug Therapy

Keywords

  • Chemotherapy
  • Clinical trial
  • Inhibitor
  • Topoisomerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

A Phase II study of 9-nitro-camptothecin in patients with previously treated metastatic breast cancer. / Miller, Kathy; Soule, Sharon E.; Haney, LaTrice G.; Guiney, Patricia; Murry, Darryl J.; Lenaz, Luigi; Sun, Show Li; Sledge, George W.

In: Investigational New Drugs, Vol. 22, No. 1, 01.2004, p. 69-73.

Research output: Contribution to journalArticle

Miller, Kathy ; Soule, Sharon E. ; Haney, LaTrice G. ; Guiney, Patricia ; Murry, Darryl J. ; Lenaz, Luigi ; Sun, Show Li ; Sledge, George W. / A Phase II study of 9-nitro-camptothecin in patients with previously treated metastatic breast cancer. In: Investigational New Drugs. 2004 ; Vol. 22, No. 1. pp. 69-73.
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