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

Kathy D. Miller, Sharon E. Soule, La Trice G. Haney, Patricia Guiney, Daryl 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 (US)
Pages (from-to)69-73
Number of pages5
JournalInvestigational New Drugs
Volume22
Issue number1
DOIs
StatePublished - Jan 1 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

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

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

In: Investigational New Drugs, Vol. 22, No. 1, 01.01.2004, p. 69-73.

Research output: Contribution to journalArticle

Miller, Kathy D. ; Soule, Sharon E. ; Haney, La Trice G. ; Guiney, Patricia ; Murry, Daryl 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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