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Phase
I study of intrathecal (IT) Spartaject busulfan (Bu) in children with neoplastic
meningitis (NM): A Pediatric Brain Tumor Consortium Trial
S.
Gururangan, H. S. Friedman, P. C. Phillips, W. Petros, S. M. Blaney, D. Hunt, L.
E. Kun
for
the Pediatric Brain Tumor Consortium (PBTC); Duke University Medical Center,
Durham, NC; Children's Hospital of Philadelphia, Philadelphia, PA; Mary Babb
Randolph Cancer Center, Morgantown, WV; Texas Children's Hospital, Houston, TX;
St. Jude Children's Research Hospital, Memphis, TN.
The
Pediatric Brain Tumor Consortium is currently conducting a phase I study of
intrathecal Bu, a novel Bu formulation in children with NM.
IT Bu is administered via an Ommaya reservoir (OR) and/or lumbar puncture twice
weekly for 2 weeks followed by an assessment of toxicity and response to
treatment.
Patients with stable disease (SD) or a response may continue to receive IT Bu +
systemic chemotherapy at regular intervals.
Cerebrospinal fluid (CSF) and blood are obtained for PK studies in patients with
OR after both an OR and an intralumbar dose.
26 pts (median age 10.1 yrs, range 2.6 to 19.5) are enrolled with a predominant
histologic diagnosis of primitive neuroectodermal tumor (58%).
The starting dose was 5 mg (n=7) with subsequent escalations to 7.5 mg (n=2), 10
mg (n=3), 13 mg (n=7) and 17 mg (n=7).
Dose escalations have been determined by the modified continual reassessment
method.
DLT has been observed in 3/19 pts who are evaluable for toxicity.
DLTs include grade III vomiting (n=1 at 5 mg), grade III headache (n=1 at 17
mg), and grade III arachnoiditis (n=1 at 17 mg).
Two pts with SD continue to receive IT Bu for 7+ and 14+ months.
PK data is currently available on 3 pts at the 5 mg (n= 2) and 7.5 mg (n= 1)
dose levels.
High concentrations of Bu were found in the ventricular CSF samples with peak
values reaching 52 to 106 mcg/ml.
These declined to < 1 mcg/ml within 5 hours.
Additional PK data will be presented at the meeting.
In conclusion, IT Bu is well-tolerated in children with NM.
Further accrual is ongoing in an expanded cohort to confirm the MTD of 13 mg.
© Copyright 2003
American Society of
Clinical Oncology All rights reserved worldwide
Source: http://www.asco.org/ac/1,1003,_12-002489-00_18-002003-00_19-00103663-00_29-00A,00.asp?cat=CNS+Tumors&parent=
Central+Nervous+System+Tumors&returnpid=2325&SubCat_ID=4 |
