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


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.


CONCLUSIONS
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.
Blaney
Susan M
SM
Texas Children's Cancer Center/Baylor College of Medicine, Houston, TX 77030, USA. sblaney@txccc.org
Heideman
Richard
R
Berg
Stacey
S
Adamson
Peter
P
Gillespie
Andy
A
Geyer
J Russell
JR
Packer
Roger
R
Matthay
Kate
K
Jaeckle
Kurt
K
Cole
Diane
D
Kuttesch
Nancy
N
Poplack
David G
DG
Balis
Frank M
FM
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D019772:Topotecan / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019772:Topotecan