RTOG 0211: A Phase 1/2 Study of Radiation Therapy With Concurrent Gefitinib for Newly Diagnosed Glioblastoma Patients

Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University, Columbus, Ohio. Electronic address: .
International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 11/2012; 85(5). DOI: 10.1016/j.ijrobp.2012.10.008
Source: PubMed


To determine the safety and efficacy of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with radiation for newly diagnosed glioblastoma (GBM) patients.

Methods and materials:
Between March 21, 2002, and May 3, 2004, Radiation Therapy Oncology Group (RTOG) 0211 enrolled 31 and 147 GBM patients in the phase 1 and 2 arms, respectively. Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy (RT) and continued post RT for 18 months or until progression. Tissue microarrays from 68 cases were analyzed for EGFR expression.

The maximum tolerated dose (MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs (non-EIAEDs). All patients in the phase 2 component were treated at a gefitinib dose of 500 mg; patients receiving EIADSs could be escalated to 750 mg. The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal. Median survival was 11.5 months for patients treated per protocol. There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone, matched by RTOG recursive partitioning analysis (RPA) class distribution. Younger age was significantly associated with better outcome. Per protocol stratification, EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients.

The addition of gefitinib to RT is well tolerated. Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone.

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Available from: Minesh P Mehta, Feb 18, 2015
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    • "2010 II NSCLC 66 Gy þ gefitinib after induction chemotherapy Survival of poor-risk patients was promising, but for good-risk patients was disappointing. Gefitinib [29] 2011 II HNSCC 70 Gy þ cisplatin þ gefitinib Well tolerated but did not improve efficacy Gefitinib [30] 2012 II NSCLC þ brain metastasis 30 Gy þ gefitinib or temozolomide Well tolerated but study did not support use of combination as PFS and OS poor Gefitinib [31] 2013 I/II Glioblastoma 60 Gy þ gefitinib Well tolerated, no improvement in outcome Lapatinib [32] 2012 I Breast 35e70 Gy þ lapatinib Well tolerated, response rates comparable to other studies NSCLC, non-small cell lung cancer; HNSCC, head and neck squamous cell carcinoma; 5-FU, 5-fluorouracil; IR, irradiation (dose variable); CRR, complete remission rate; PFS, progression-free survival; CR, complete remission, QoL, quality of life; OS, overall survival. "
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    Clinical Oncology 03/2014; 26(5). DOI:10.1016/j.clon.2014.02.006 · 3.40 Impact Factor
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    • "Unfortunately, early clinical results have been disappointing. Recent early phase trials from the RTOG and Mayo/North American Cancer Treatment group have shown no survival benefit in patients receiving gefitinib with irradiation when compared to historic controls (19, 20). "
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    • "Regarding TKIs, Chakravarti et al. reported no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone [47] and a recent phase II clinical trial for GBM therapy, erlotinib was well tolerated, but only demonstrated a modest effect over placebo [48]. "
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