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

Susan M. Blaney, Richard Heideman, Stacey Berg, Peter Adamson, Andy Gillespie, J. Russell Geyer, Roger Packer, Kate Matthay, Kurt Jaeckle, Diane Cole, Nancy Kuttesch, David G. Poplack, Frank M. Balis

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Purpose: A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis. Patients and Methods: Twenty-three assessable patients received IT topotecan administered by means of either lumbar puncture or an indwelling ventricular access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to 0.2 mg was performed in the first cohort of patients. Subsequent cohorts of patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results: Arachnoiditis, characterized by fever, nausea, vomiting, headache, and back pain, was the dose-limiting toxic effect in two of four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD) was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested as prolonged disease stabilization or response. Conclusion: The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress. J Clin Oncol 21:143-147.

Original languageEnglish (US)
Pages (from-to)143-147
Number of pages5
JournalJournal of Clinical Oncology
Issue number1
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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