PMID- 19960228 OWN - NLM STAT- MEDLINE DCOM- 20100908 LR - 20231120 IS - 1573-7373 (Electronic) IS - 0167-594X (Linking) VI - 98 IP - 1 DP - 2010 May TI - Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme. PG - 93-9 LID - 10.1007/s11060-009-0067-2 [doi] AB - 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. FAU - Peereboom, David M AU - Peereboom DM AD - Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. peerebd@ccf.org FAU - Shepard, Dale R AU - Shepard DR FAU - Ahluwalia, Manmeet S AU - Ahluwalia MS FAU - Brewer, Cathy J AU - Brewer CJ FAU - Agarwal, Neeraj AU - Agarwal N FAU - Stevens, Glen H J AU - Stevens GH FAU - Suh, John H AU - Suh JH FAU - Toms, Steven A AU - Toms SA FAU - Vogelbaum, Michael A AU - Vogelbaum MA FAU - Weil, Robert J AU - Weil RJ FAU - Elson, Paul AU - Elson P FAU - Barnett, Gene H AU - Barnett GH LA - eng PT - Clinical Trial, Phase II PT - Journal Article DEP - 20091204 PL - United States TA - J Neurooncol JT - Journal of neuro-oncology JID - 8309335 RN - 0 (Antineoplastic Agents, Alkylating) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - 0 (Tumor Suppressor Proteins) RN - 7GR28W0FJI (Dacarbazine) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.1.1.- (DNA Modification Methylases) RN - EC 2.1.1.63 (MGMT protein, human) RN - EC 6.5.1.- (DNA Repair Enzymes) RN - YF1K15M17Y (Temozolomide) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antineoplastic Agents, Alkylating/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Brain Neoplasms/*drug therapy/*radiotherapy MH - DNA Modification Methylases/metabolism MH - DNA Repair Enzymes/metabolism MH - Dacarbazine/analogs & derivatives/therapeutic use MH - Disease-Free Survival MH - Erlotinib Hydrochloride MH - Female MH - Glioblastoma/*drug therapy/*radiotherapy MH - Humans MH - Karnofsky Performance Status MH - Magnetic Resonance Imaging/methods MH - Male MH - Methylation/drug effects/radiation effects MH - Middle Aged MH - Protein Kinase Inhibitors/therapeutic use MH - Quinazolines/therapeutic use MH - Radiotherapy/*methods MH - Temozolomide MH - Tumor Suppressor Proteins/metabolism MH - Young Adult EDAT- 2009/12/05 06:00 MHDA- 2010/09/09 06:00 CRDT- 2009/12/05 06:00 PHST- 2009/07/23 00:00 [received] PHST- 2009/11/09 00:00 [accepted] PHST- 2009/12/05 06:00 [entrez] PHST- 2009/12/05 06:00 [pubmed] PHST- 2010/09/09 06:00 [medline] AID - 10.1007/s11060-009-0067-2 [doi] PST - ppublish SO - J Neurooncol. 2010 May;98(1):93-9. doi: 10.1007/s11060-009-0067-2. Epub 2009 Dec 4.