A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM).
Twenty-two patients with recurrent glioblastoma (GBM) were prospectively treated with everolimus and gefitinib, designed to test the combined inhibition of mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR) as part of a larger clinical trial. The primary endpoint was radiographic response rate. Secondary endpoints included progression-free survival and correlation of molecular profiles with treatment response. 36% of patients had stable disease and 14% a partial response; however, responses were not durable and only one patient was progression-free at six months. Radiographic changes were not well characterized by conventional response criteria, and implied differential effects of therapy within the tumor and/or antiangiogenic effects. EGFR and PTEN status did not clearly predict response to treatment.
Kreisl
Teri N
TN
Neuro-Oncology Branch, National Cancer Institute, 9030 Old Georgetown Road, Bethesda, MD 20892, USA.
Lassman
Andrew B
AB
Mischel
Paul S
PS
Rosen
Neal
N
Scher
Howard I
HI
Teruya-Feldstein
Julie
J
Shaffer
David
D
Lis
Eric
E
Abrey
Lauren E
LE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis; D000068338:Everolimus; D005260:Female; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D010865:Pilot Projects; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D011799:Quinazolines; D000068338:Everolimus; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077156:Gefitinib; D020123:Sirolimus