Temozolomide with Radiotherapy Safer, Equally Effective as Nitrosureas for Anaplastic Astrocytoma
Radiotherapy plus temozolomide did not appear to significantly improve survival for anapestic astrocytoma compared with nitrosurea.
CHICAGO–Radiotherapy plus temozolomide did not appear to significantly improve overall survival or time to tumor progression for anaplastic astrocytoma compared with radiotherapy plus nitrosurea therapy, but radiotherapy plus temozolomide was better tolerated, a study presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting has shown.
“Previous studies have demonstrated survival benefit for adjuvant nitrosurea in anaplastic glioma,” said Susan M. Chang, MD, Director of Neuro-Oncology at the University of California, San Francisco. No previous studies have compared the efficacy of temozolomide to nitrosurea in newly diagnosed anaplastic astrocytoma treated with radiotherapy.”
For the study, researchers enrolled 201 patients with anaplastic astrocytoma and randomly assigned them 1:1 to receive radiotherapy 59.4 Gy with temozolomide 200 mg/m2 daily on days 1 to 5 of the first week of radiotherapy for 6 weeks, with adjuvant temozolomide every 28 days for 12 cycles or nitrosurea therapy (BCNU or CCNU).
“Patients characteristics were balanced across both arms in terms of prognostic factors and stratification factors,” Dr. Chang added. Chemotherapy was only completed as planned in 60.4% and 21.4% of the temozolomide and nitrosurea patients, respectively.
Results showed that there was no difference in overall survival between the radiotherapy plus temozolomide arm compared with the radiotherapy plus nitrosurea arm (P=0.37), where median survival time was 3.9 years (95% CI: 3.0, 7.0) for radiotherapy plus temozolomide and 3.8 years (95% CI: 2.2, 7.0) for radiotherapy plus nitrosurea (HR=0.94; 95% CI: 0.67, 1.33).
Researchers also found that progression-free survival and time-to-treatment failure did not differ between the two arms (P=0.32).
In addition, molecular correlative studies demonstrated that IDH mutation and ATRX mutation were prognostic factors, but future studies to further explore this association are pending.
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In regard to safety, radiotherapy plus nitrosurea therapy was associated with a higher incidence of worse overall grade 3 or higher toxicity compared with the radiotherapy plus temozolomide arm (75.8% vs. 47.9%; P<0.001). Most grade 3 or higher toxicities were related to myelosuppression.
The trial was ultimately closed early due to failure to meet accrual goals.
Dr. Chang concluded, “Radiotherapy plus temozolomide did not significantly improve overall survival for patients with anaplastic astrocytoma, as compared with radiotherapy plus nitrosurea. The differences in progression-free survival and time-to-treatment failure between the two treatment arms were not statistically significant.”
- Chang SM, Zhang P, Cairncross JG, et al. Results of NRG oncology/RTOG 9813: A phase III randomized study of radiation therapy (RT) and temozolomide (TMZ) versus RT and nitrosourea (NU) therapy for anaplastic astrocytoma (AA). J Clin Oncol. 2015;33:(suppl; abstr 2002).