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Imatinib Inactive in Sarcomas That Lack C-KIT/PDGF

Imatinib Inactive in Sarcomas That Lack C-KIT/PDGF

ORLANDO—The tyrosine
inhibitor imatinib mesylate (Gleevec) is active in gastrointestinal stromal
tumors (GISTs) but not in other soft-tissue sarcomas not characterized by C-KIT
or PDGF-R expression, the targets of imatinib, Ian R. Judson, MD, said at the
American Society of Clinical Oncology annual meeting (abstract 1609).

Dr. Judson reported phase II data on behalf of the European
Organization for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone
Sarcoma Group. He is a medical oncologist at the Royal Marsden Hospital,

The multicenter study enrolled 27 patients with GIST and 24
with CD117-negative non-GIST soft-tissue sarcomas. (CD117 is a marker for KIT.)
GISTs were required to be KIT positive. All patients had locally advanced
unresectable and/or metastatic disease. About half of the GIST patients (52%)
and most of the non-GIST patients (92%) had received prior chemotherapy.

The non-GIST soft-tissue sarcoma patients tended to have
pulmonary metastases, but few of the GIST patients had lung lesions. Liver
metastases were present in the minority of the non-GIST population but in most
GIST patients.

Patients came off treatment quickly in the non-GIST group
but tended to continue imatinib for long periods in the GIST population.

The most common side effects were anemia, granulocytopenia,
edema, fatigue, rash, and nausea. Grade 3-4 toxicities were rare and generally
not a problem at the dose used (800 mg daily). Grade 2 anemia, edema, and
fatigue were relatively common.

"It was our clinical impression that some of the toxicities
we observed tended to become less severe with prolonged treatment. This was the
case for edema, where gradually the grade 2 toxicity faded away leaving just a
little grade 1 periorbital edema, which some patients never lose," Dr. Judson
said. Skin rash similarly occurred up to grade 3 toxicity levels but tended to
disappear with time. Nausea also tended to resolve over time.


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