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A
phase I trial of continuously infused intratumoral bleomycin for the treatment
of recurrent glioblastoma multiforme
Patchell
RA, Regine WF, Ashton P, Tibbs PA, Wilson D, Shappley D, Young B
Department
of Neurology, University of Kentucky Medical Center, Lexington 40536, USA.
rpatchell@aol.com
Intratumoral
(IT) chemotherapy has theoretical advantages in the treatment of brain tumors.
The blood-brain barrier is not a factor in drug delivery, and large
concentrations of drug can be instilled in the tumor with little systemic
toxicity.
Bleomycin has activity against gliomas and is a cell cycle selective
agent whose efficacy should be enhanced by continuous infusion.
We performed a
phase I trial to test the feasibility of IT chemotherapy using a refillable,
sustained release device, and to determine the maximum tolerable dose of IT
bleomycin.
The study was an open-ended dose escalation study.
A modified Ommaya
reservoir (containing a semipermeable membrane) was implanted with the delivery
tube in the center of the tumor.
Groups of three patients with recurrent
glioblastoma multiforme were entered at progressively higher dose levels of
bleomycin. The study closed when all patients at a given starting dose level
developed toxicity.
Nine patients received doses ranging from 5 to 34 U/wk; the
median total cumulative dose was 195 U. No dose limiting systemic toxicity was
detected.
Neurologic toxicity occurred only at doses above 16 U/wk.
We conclude
that continuously infused IT bleomycin is well tolerated; the MTD (and
recommended dose for a phase II efficacy trial) of IT bleomycin is 16 U/wk.
PMID: 12416544 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12416544&dopt=Abstract |
