Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis

Ronald J. Bernardi, Lisa Bomgaars, Elizabeth Fox, Frank M. Balis, Merrill J. Egorin, Theodore F. Lagattuta, Alberta Aikin, Patricia Whitcomb, Jamie Renbarger, Frank S. Lieberman, Stacey L. Berg, Susan M. Blaney

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18 Scopus citations


Purpose: A phase I study of intrathecal (IT) gemcitabine was performed to define a safe dose and characterize the toxicity profile and CSF pharmacokinetics of gemcitabine and its major metabolite 2′,2′- difluoro-deoxyuridine (dFdU) in patients 3 years of age and older with neoplastic meningitis. Experimental design: Gemcitabine was administered via Ommaya reservoir or lumbar puncture at three dose levels: 5 mg weekly, 5 mg twice-weekly, and 10 mg twice-weekly using a standard phase I dose escalation design. Serial CSF samples were obtained for pharmacokinetic studies in seven patients with Ommaya reservoirs. Serial blood samples for pharmacokinetic studies were also obtained from three patients. Results: Ten patients were enrolled in this study. Significant neurological toxicities occurred in two patients including myelitis in a patient at the 5 mg twice-weekly dose level and somnolence in a patient at the 10 mg twice-weekly dose level. No complete responses were seen; however, three patients had stable disease. Gemcitabine was rapidly eliminated from the CSF with a terminal half-life of 61 ± 50 min. No gemcitabine or dFdU was detected in plasma. Conclusions: IT gemcitabine was associated with significant neurotoxicity; therefore, its further development for IT use is not recommended.

Original languageEnglish (US)
Pages (from-to)355-361
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Issue number2
StatePublished - Jul 2008


  • Gemcitabine
  • Intrathecal
  • Pharmacokinetic
  • Phase I

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

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    Bernardi, R. J., Bomgaars, L., Fox, E., Balis, F. M., Egorin, M. J., Lagattuta, T. F., Aikin, A., Whitcomb, P., Renbarger, J., Lieberman, F. S., Berg, S. L., & Blaney, S. M. (2008). Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemotherapy and Pharmacology, 62(2), 355-361.