A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas.
When surgery and radiation are no longer treatment options, salvage systemic therapy has been used for recurrent meningiomas with little compelling evidence to suggest effectiveness. Patients with surgery and radiation refractory recurrent meningiomas were treated with the oral multifunctional tyrosine kinase inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each treatment cycle was 4 weeks with MRI done every 8 weeks. Twenty-five patients (14 men; 11 women) with a median age of 59 years and KPS of 80 were treated. Meningioma WHO Grade was I in 2 patients, II in 14 patients and III in 8 patients; 1 patient had a hemangiopericytoma. All patients had prior surgery, external beam radiation therapy or radiosurgery and 11 patients prior systemic chemotherapy. Median number of cycles of PTK 787 administered was 4 (range <1-22). Best response in the 22 evaluable patients was stable disease in 15 (68.2 %). Predominant PTK787 related toxicities included fatigue (60 %), hypertension (24 %) and elevated transaminases (24 %). Grade II patients had a progression free survival (PFS)-6 of 64.3 %, a median PFS of 6.5 months and an overall survival (OS) of 26.0 months; grade III patients had a PFS-6 of 37.5 %, median PFS of 3.6 months and OS 23 months. PTK787 was modestly toxic at the dose of 500 mg administered twice per day. Activity as determined by PFS-6 suggests that targeting PDGF/VEGF pathway warrants further investigation.
Department of Neurology, Northwestern University, 710 North Lake Shore Drive-Abbott Hall Room 1123, Chicago, IL, 60611, USA, jraizer@nmff.org.
Jeffrey J
JJ
Raizer
Sean A
SA
Grimm
Alfred
A
Rademaker
James P
JP
Chandler
Kenji
K
Muro
Irene
I
Helenowski
Laurie
L
Rice
Katie
K
McCarthy
Sandra K
SK
Johnston
Maciej M
MM
Mrugala
Marc
M
Chamberlain
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008579:Meningioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010793:Phthalazines / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy; D013997:Time Factors
D000970:Antineoplastic Agents; D010793:Phthalazines; D011725:Pyridines; C404768:vatalanib