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Mesothelioma
Treatment
Articles
and Abstracts
Intralesional
cytokine therapy in cancer: a pilot study
of GM-CSF infusion in mesothelioma.
J
Immunother 1998 Sep;21(5):389-98
Davidson
JA, Musk AW, Wood BR, Morey S, Ilton M, Yu
LL, Drury P, Shilkin K, Robinson
B
University
Department of Medicine, Sir Charles
Gairdner Hospital, Queen Elizabeth II
Medical Centre, Perth, Australia.
Systemic
cytokine therapy in cancer has major side
effects, and we reasoned that the local
infusion of cytokines into tumors could
induce local immunologic responses with
minimal toxicity and potentially strong
systemic anticancer effects. This study
investigated the toxicity and
effectiveness of intralesional
granulocyte/macrophage-colony-stimulating
factor (GM-CSF) infusion in solid-tumor
masses. We studied 14 patients (12 men,
two women) with malignant mesothelioma
(MM), aged 60 years (range, 46-70 years),
with stage 2 disease, in whom the tumor
was of sufficient size and accessibility
for an intralesional catheter to be
inserted. Recombinant human GM-CSF
(Molgramostim; Schering Plough) was
infused intralesionally for 8 weeks, by
using a portable pump, at a dose of 2.5-10
micrograms/kg/day. One patient using
GM-CSF developed histologically confirmed
necrosis of tumor surrounding the distal
catheter, one developed a marked
lymphocytic infiltrate in the tumor and
had a partial response measured by chest
computed tomography (CT) scan, 10
progressed, and three had no response.
Neutrophilia with morphologic evidence of
neutrophil activation and clinical
features suggestive of neutrophil plugging
of blood vessels occurred at doses > 5
micrograms/kg/day. In vitro, GM-CSF
doubled human neutrophil/CD11b/CD18
expression, suggesting that neutrophil
clumping as seen in vivo might be due to
integrin upregulation. Intralesional
infusion of cytokines is feasible but can
be associated with systemic toxicity and
has considerable technical problems. It
produces a localized immune reaction with
tumor regression in a minority of
patients.
PMID:
9789201, UI: 99005630
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