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Cancer Chemother Pharmacol. 2008 Jul;62(2):355-61. Epub 2007 Oct 2.

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

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1
Texas Children's Hospital, Baylor College of Medicine, Houston, TX, 77030, USA.

Abstract

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.

PMID:
17909804
DOI:
10.1007/s00280-007-0601-x
[Indexed for MEDLINE]

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