Cancer Chemotherapy and Pharmacology

, Volume 46, Issue 5, pp 382–386 | Cite as

Phase II trial and pharmacokinetic evaluation of cytosine arabinoside for leptomeningeal metastases from breast cancer

  • Francisco J. Esteva
  • Lay-Tin Soh
  • Frankie Ann Holmes
  • William Plunkett
  • Christina A. Meyers
  • Arthur D. Forman
  • Gabriel N. Hortobagyi
ORIGINAL ARTICLE

Abstract

Purpose: To determine the efficacy and pharmacokinetics of intraventricular cytosine arabinoside (Ara-C) as front-line treatment for leptomeningeal metastases from breast cancer. Methods: Ten patients newly diagnosed with leptomeningeal metastases (LMM) from breast cancer were treated with 100 mg intraventricular cytosine arabinoside (IVT Ara-C) via an Ommaya reservoir. Treatment was administered three times a week for 2 weeks, then once a week for 4 weeks, and then once every 6 weeks for four cycles to responding patients. Nine patients were evaluable clinically, and seven patients underwent testing to determine the pharmacokinetic profile of Ara-C in the cerebrospinal fluid (CSF). Results: Two patients had partial responses lasting 9 and 40 weeks, respectively. Two other patients had stable disease. The median survival duration was 30 weeks (range: 5–58 weeks). Seven patients died from LMM. Acute toxic effects associated with IVT Ara-C included meningismus, nausea, vomiting, and myelosuppression. The median peak Ara-C level in CSF was 16.69 ± 6.30 mM (SD). The half life for elimination was 1.45 ± 0.61 h (SD) There was no drug accumulation between courses. Neuropsychological evaluations were completed in eight patients, six (75%) of whom had preexisting cognitive deficits. Their condition generally improved over the course of treatment until the LMM progressed. No neurotoxic side effects of IVT Ara-C were observed in the two patients who had normal baseline cognitive assessments. Conclusions: IVT Ara-C at this dose and schedule has minimal activity as initial treatment for LMM from breast cancer despite achievement of high peak levels of the drug in the cerebrospinal fluid. A liposomal Ara-C formulation is currently under investigation.

Key words Breast neoplasms Meningeal neoplasms Cytosine arabinoside Treatment 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Francisco J. Esteva
    • 1
  • Lay-Tin Soh
    • 1
  • Frankie Ann Holmes
    • 1
  • William Plunkett
    • 2
  • Christina A. Meyers
    • 3
  • Arthur D. Forman
    • 3
  • Gabriel N. Hortobagyi
    • 1
  1. 1.Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 56, Houston, TX 77030-4095, USA Tel.: +1-713-7922817; Fax: +1-713-7944385US
  2. 2.Department of Clinical Investigation, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USAUS
  3. 3.Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USAUS

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