TY - JOUR
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.
N1 - Publisher Copyright:
© 2003 by American Society of Clinical Oncology.
PY - 2003/1/1
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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U2 - 10.1200/JCO.2003.04.053
DO - 10.1200/JCO.2003.04.053
M3 - Article
C2 - 12506183
AN - SCOPUS:18744402164
SN - 0732-183X
VL - 21
SP - 143
EP - 147
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -