title: Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme.
abstract: Approximately 40-50% of glioblastomas (GBM) overexpress epidermal growth factor receptor (EGFR). Erlotinib is a specific and potent EGFR tyrosine kinase inhibitor active against refractory GBM. Patients with non-small cell lung cancer and > or =grade 2 erlotinib-induced rash have improved survival. This phase 2 study assessed the efficacy and safety of concurrent radiation therapy (RT) and temozolomide with pharmacodynamic dose escalation of erlotinib in patients with newly diagnosed GBM. Patients received RT 60 Gy in 30 fractions with concurrent temozolomide 75 mg/m(2)/day x 42 days, followed in four weeks by temozolomide 150-200 mg/m(2)/day x 5, every 28 days for 12 cycles. Patients received erlotinib, 50 mg/day and increased by 50 mg/day every 2 weeks until the occurrence of grade 2 rash or to a maximum dose of 150 mg/day, from day 1 until disease progression. Twenty-seven patients were treated in this study. Twenty-two (81%) patients came off study for progressive disease (18 [67%]) or adverse events (4 [15%]). Eighteen patients (67%) have died. Median progression-free survival was 2.8 months, and the median overall survival was 8.6 months. Five patients remain on study with a median follow-up of 16 months. Grade 3/4 toxicities included thrombocytopenia, anemia, lymphopenia, fatigue, and febrile neutropenia. There were four deaths on study, three definitely treatment-related; therefore, the trial was terminated after accrual of 27 of 30 planned patients. Erlotinib co administered with RT and temozolomide was not efficacious and had an unacceptable toxicity.
authors: Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. peerebd@ccf.org
authors: David M
authors: DM
authors: Peereboom
authors: Dale R
authors: DR
authors: Shepard
authors: Manmeet S
authors: MS
authors: Ahluwalia
authors: Cathy J
authors: CJ
authors: Brewer
authors: Neeraj
authors: N
authors: Agarwal
authors: Glen H J
authors: GH
authors: Stevens
authors: John H
authors: JH
authors: Suh
authors: Steven A
authors: SA
authors: Toms
authors: Michael A
authors: MA
authors: Vogelbaum
authors: Robert J
authors: RJ
authors: Weil
authors: Paul
authors: P
authors: Elson
authors: Gene H
authors: GH
authors: Barnett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008745:Methylation / Q000187:drug effects / Q000528:radiation effects; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D011878:Radiotherapy / Q000379:methods*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D000069347:Erlotinib Hydrochloride; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide