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Long-term treatment of malignant gliomas with intramuscularly
administered polyinosinic-polycytidylic acid stabilized with polylysine and
carboxymethylcellulose: an open pilot study
Salazar AM, Levy HB, Ondra S, Kende M, Scherokman B, Brown D, Mena H, Martin
N, Schwab K, Donovan D, Dougherty D, Pulliam M, Ippolito M, Graves M, Brown H,
Ommaya A.
Uniformed Services University of the Health Sciences, Washington, District of
Columbia, USA.
Polyinosinic-polycytidylic acid stabilized with polylysine and
carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly
one to three times weekly) was given for < or = 56 months to 38 patients with
malignant gliomas. There was minimal or no toxicity.
Twenty of 30 patients (66%)
receiving at least twice weekly poly-ICLC showed regression or stabilization of
gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median =
65% volume decrease).
All but one patient with anaplastic astrocytomas who
received continuous poly-ICLC remain alive, with a median progression-free
survival of 54 months from diagnosis.
Median Kaplan-Meier survival is 19 months
for patients with glioblastomas who receive at least twice weekly poly-ICLC
treatments.
Tumor response was associated with 2',5' -oligoadenylate synthetase
activation (P = 0.03) but not with serum interferon.
We hypothesize clinical
activation by poly-ICLC of a basic host tumor suppressor system.
Prolonged,
quality survival with tumor stabilization or regression confirmed by magnetic
resonance imaging for most patients with anaplastic astrocytomas and
glioblastomas suggests that more extensive laboratory and controlled clinical
studies are warranted.
The concept of long-term, broad spectrum stimulation of
host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such
as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.
PMID: 8727138 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8727138&dopt=Abstract
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