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Response
of cerebellar hemangioblastomas associated with von Hippel-Lindau disease to
OSI-774 (TarcevaTM)
Lisa R
Rogers, William Kaelin, Paul Nadler, Anthony F Shields, Patricia LoRusso
Henry
Ford Hosp, Detroit, MI; Dana-Farber Cancer Inst, Boston, MA; OSI
Pharmaceuticals, Melville, NY; Karmanos Cancer Institute, Detroit, MI.
Von
Hippel-Lindau (VHL) disease is a genetic disorder that is associated with a
variety of malignancies, including central nervous system hemangioblastoma (HB).
Overexpression of EGFR and TGF-alpha are hallmarks of VHL-associated neoplasms,
including HBs.
HBs are typically localized to the cerebellum and cervical spine and treatment
is surgical resection and/or radiation.
We report a 37 year old patient with VHL who had progression of cerebellar HBs
in association with leptomeningeal metastasis following surgical resection,
stereotactic radiosurgery, and external beam radiation.
MRI showed multiple cerebellar and spine HBs and diffuse leptomeningeal
metastasis.
CSF showed elevated protein and 20 WBC/mm3.
She received OSI-774 because it is a selective EGFR tyrosine kinase inhibitor,
as part of an ongoing Fluorothymidine PET study being performed at Karmanos
Cancer Institute.
The daily dose was 150 mg.
Neurological symptoms improved within one month of treatment although the
neurological examination remained stable.
The PET scan was stable at 2 weeks.
Her best response was a minor response of 2 cerebellar HBs on MRI and the CSF
WBC normalized to 4/mm3.
Minimal toxicity was noted, including skin rash, loose stools, and dry eyes.
She remained on study for 9 months, until progression.
Plasma and CSF drug levels and pharmacodynamic endpoints will be presented.
Our experience suggests that OSI-774 may have antitumor activity in HBs
associated with VHL.
© Copyright 2002
American
Society of Clinical Oncology
Source: http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-002111-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
&returnpid=2323
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