Background
CODEL (N0577) was designed to test whether temozolomide alone could replace radiotherapy-based regimens in newly diagnosed 1p/19q-codeleted grade 3 oligodendroglioma, motivated by the chemosensitivity of codeleted tumors and concerns about RT-related neurotoxicity.
Interventions and follow up
Arm A: Radiotherapy alone (59.4 Gy)
Arm B: Radiotherapy (59.4 Gy) + concurrent and adjuvant TMZ
Arm C: TMZ alone (200mg/m² days 1–5 q28d)
Primary endpoint: OS (Arm A vs B)
mFollow-up: 7.5yr (median)
Arm B: Radiotherapy (59.4 Gy) + concurrent and adjuvant TMZ
Arm C: TMZ alone (200mg/m² days 1–5 q28d)
Primary endpoint: OS (Arm A vs B)
mFollow-up: 7.5yr (median)
Results
n: 36 (initial design; trial closed early, underpowered for OS)
Progression: 83.3% (TMZ-alone) vs 37.5% (RT arms)
PFS: significantly shorter with TMZ alone (HR 3.12, 95% CI 1.26–7.69, P=.014)
OS: no statistical difference (HR 2.78, P=.20; underpowered)
Salvage: most TMZ-alone patients required salvage RT
Progression: 83.3% (TMZ-alone) vs 37.5% (RT arms)
PFS: significantly shorter with TMZ alone (HR 3.12, 95% CI 1.26–7.69, P=.014)
OS: no statistical difference (HR 2.78, P=.20; underpowered)
Salvage: most TMZ-alone patients required salvage RT
Adverse events
Overall (grade ≥3): 25% (RT alone), 42% (RT+TMZ), 33% (TMZ alone)
Hematologic: myelosuppression more common in chemotherapy-containing arms; neurocognitive deterioration at 3 months similar across arms.
Hematologic: myelosuppression more common in chemotherapy-containing arms; neurocognitive deterioration at 3 months similar across arms.
Conclusions
In 1p/19q-codeleted oligodendroglioma, omitting radiotherapy in favor of TMZ alone produced significantly shorter PFS and more frequent salvage interventions. These data do not support TMZ alone as a first-line alternative to RT; the trial was redesigned to compare RT+PCV vs RT+TMZ.
Key Limitations
Original design closed early with only 36 patients, leaving it underpowered for OS and yielding only hypothesis-generating data. Short follow-up relative to the indolent natural history of codeleted oligodendroglioma. The redesigned RT+PCV vs RT+TMZ comparison addresses the more clinically relevant question.
Clinical Context
CODEL reinforced that radiotherapy should not be omitted in 1p/19q-codeleted oligodendroglioma. ESMO and ASCO/SNO guidelines endorse RT followed by chemotherapy (PCV per RTOG 9402/EORTC 26951, or TMZ) for grade 3 codeleted disease, with RT+PCV vs RT+TMZ being addressed by the ongoing redesigned trial.