1. CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design
- Author
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David Schiff, Kurt A. Jaeckle, Evanthia Galanis, Kenneth Aldape, Donald Nordstrom, Stuart A. Grossman, Jeffrey S. Wefel, J. Gregory Cairncross, Michael A. Vogelbaum, Karla V. Ballman, F. Dhermain, Michael Weller, Martin Klein, Patrick J. Flynn, Wolfgang Wick, Paul D. Brown, S. Keith Anderson, Robert B. Jenkins, Caterina Giannini, Jesse G. Dixon, Jeffrey Raizer, Martin J. van den Bent, Jane H. Cerhan, Medical psychology, CCA - Cancer Treatment and quality of life, Neurology, Jaeckle K.A., Ballman K.V., Van Den Bent M., Giannini C., Galanis E., Brown P.D., Jenkins R.B., Cairncross J.G., Wick W., Weller M., Aldape K.D., Dixon J.G., Anderson S.K., Cerhan J.H., Wefel J.S., Klein M., Grossman S.A., Schiff D., Raizer J.J., Dhermain F., Nordstrom D.G., Flynn P.J., and Vogelbaum M.A.
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Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,N0577 ,Oligodendroglioma ,Clinical Investigations ,Brain Neoplasm ,SDG 3 - Good Health and Well-being ,Internal medicine ,CODEL ,Clinical endpoint ,1p/19q ,Temozolomide ,Medicine ,Humans ,Adverse effect ,business.industry ,Proportional hazards model ,Brain Neoplasms ,Hazard ratio ,medicine.disease ,Isocitrate Dehydrogenase ,Progression-Free Survival ,Radiation therapy ,Dacarbazine ,codeleted ,Concomitant ,Neurology (clinical) ,business ,medicine.drug ,Human - Abstract
Background We report the analysis involving patients treated on the initial CODEL design. Methods Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. Results Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. Conclusions TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.
- Published
- 2021
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