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 journalArticle

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Abstract

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
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2003

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Topotecan
Clinical Trials, Phase I
Meningitis
Poisons
Maximum Tolerated Dose
Arachnoiditis
Spinal Puncture
Back Pain
Nausea
Vomiting
Headache
Fever
Pharmacokinetics
Equipment and Supplies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Blaney, S. M., Heideman, R., Berg, S., Adamson, P., Gillespie, A., Geyer, J. R., ... Balis, F. M. (2003). Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. Journal of Clinical Oncology, 21(1), 143-147. https://doi.org/10.1200/JCO.2003.04.053
Blaney, Susan M. ; Heideman, Richard ; Berg, Stacey ; Adamson, Peter ; Gillespie, Andy ; Geyer, J. Russell ; Packer, Roger ; Matthay, Kate ; Jaeckle, Kurt ; Cole, Diane ; Kuttesch, Nancy ; Poplack, David G. ; Balis, Frank M. / Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 1. pp. 143-147.
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abstract = "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.",
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Blaney, SM, Heideman, R, Berg, S, Adamson, P, Gillespie, A, Geyer, JR, Packer, R, Matthay, K, Jaeckle, K, Cole, D, Kuttesch, N, Poplack, DG & Balis, FM 2003, 'Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis', Journal of Clinical Oncology, vol. 21, no. 1, pp. 143-147. https://doi.org/10.1200/JCO.2003.04.053

Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. / Blaney, Susan M.; Heideman, Richard; Berg, Stacey; Adamson, Peter; Gillespie, Andy; Geyer, J. Russell; Packer, Roger; Matthay, Kate; Jaeckle, Kurt; Cole, Diane; Kuttesch, Nancy; Poplack, David G.; Balis, Frank M.

In: Journal of Clinical Oncology, Vol. 21, No. 1, 01.01.2003, p. 143-147.

Research output: Contribution to journalArticle

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T1 - Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis

AU - Blaney, Susan M.

AU - Heideman, Richard

AU - Berg, Stacey

AU - Adamson, Peter

AU - Gillespie, Andy

AU - Geyer, J. Russell

AU - Packer, Roger

AU - Matthay, Kate

AU - Jaeckle, Kurt

AU - Cole, Diane

AU - Kuttesch, Nancy

AU - Poplack, David G.

AU - Balis, Frank M.

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Y1 - 2003/1/1

N2 - 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.

AB - 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.

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