Temozolomide improves short-course radiotherapy outcome in glioblastoma
medwireNews: Adding temozolomide to short-course radiotherapy significantly increases overall and progression-free survival in elderly patients with newly diagnosed glioblastoma, phase III trial data show.
Furthermore, “[t]he survival advantage of temozolomide was conferred without a sacrifice in quality of life and with manageable chemotherapy-related toxic effects,” James Perry (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada) and colleagues report in The New England Journal of Medicine.
The patients were all aged 65 years or older (median 73 years, 61% men) with newly diagnosed glioblastoma, and were deemed unsuitable by their physicians to receive conventional radiotherapy (60 Gy in 30 fractions over a period of 6 weeks) in combination with temozolomide.
They were therefore randomly assigned to receive either short-course radiotherapy alone (40 Gy in 15 fractions over 3 weeks; n=281) or with concomitant and adjuvant temozolomide (75 mg/m2 per day during radiotherapy and then up to 12 cycles of 150–200 mg/m2 daily for 5 days of a 28-day cycle; n=281).
Median overall and progression free-survival were both significantly better with radiotherapy plus temozolomide, at 9.3 and 5.3 months, respectively, than with radiotherapy alone, at 7.6 and 3.9 months.
And after adjustment for baseline clinical and demographic characteristics, radiotherapy plus temozolomide was associated with a significant 33% reduced risk for mortality and 48% reduced risk for disease progression compared with radiotherapy alone.
Perry and team also observed a possible interaction with age, whereby older patients derived the greatest benefit from the addition of temozolomide.
Specifically, patients aged 65 to 70 years who received temozolomide had a nonsignificant 7% reduced risk for death compared with those who did not, whereas the corresponding risk reduction was a significant 37% for patients aged 71 to 75 years and 47% for those aged 76 years and older.
Further subgroup analyses revealed that overall survival was significantly better with temozolomide than without it for patients with methylated O6-methylguanine–DNA methyltransferase (MGMT; 13.5 vs 7.7 months), but was only marginally better for patients with unmethylated MGMT (10.0 versus 7.9 months).
Perry et al conclude that when taken together with the results of previous studies, their “findings suggest that abbreviated radiotherapy schedules are effective and include the benefit of high completion rates and reduced treatment time for patients who often have short survival and limited mobility.”
By Laura Cowen
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