Adding Temozolomide to Short-Course RT Effective in Elderly Glioblastoma

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Elderly patients with glioblastoma had longer survival when temozolomide was added to short-course radiotherapy compared with undergoing short-course radiotherapy alone.

Elderly patients with glioblastoma had longer survival when temozolomide was added to short-course radiotherapy compared with undergoing short-course radiotherapy alone, according to the results of a study published by James R. Perry, MD, of the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, and colleagues in the New England Journal of Medicine.

The trial randomly assigned patients aged 65 or older with newly diagnosed glioblastoma to either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide. The median age of patients in the study was 73.

Among patients younger than 70, the addition of temozolomide has been shown to increase survival when added to standard radiotherapy. However, in elderly patients, shorter courses of radiotherapy are more commonly used; however, it was unknown whether the addition of temozolomide to these shorter courses of radiotherapy would confer a survival benefit.

Patients assigned to temozolomide plus radiotherapy had 33% lower risk for death compared with those who underwent radiotherapy alone (9.3 months vs 7.6 months; HR, 0.67; 95% CI, 0.56–0.80; P < .001). In an analysis that adjusted for baseline factors, the improvement in median overall survival remained significant for patients assigned temozolomide.

The researchers found that patients aged 65 to 70 years got less benefit from temozolomide than did patients aged 71 to 75, or aged 76 or older. For patients aged 65 to 70, the median overall survival was 8.7 months for radiotherapy plus temozolomide compared with 8.3 months for radiotherapy alone. In patients aged 71 to 75, the median overall survival was 9.3 months compared with 7.6 months, and in patients older than 76 the median overall survival was 10 months compared with 7.1 months.

According to the study, the decision to include patients as young as 65 was based on “current practice in our centers and on the results of previous randomized studies suggesting less benefit of radiotherapy plus temozolomide in patients 65 to 70 years of age than in younger patients.”

“We recognized that patients 65 to 70 years of age may still be offered a full 6-week course of radiotherapy plus temozolomide, so we deliberately included only patients who were deemed to be unfit for that schedule,” the researchers wrote. “It is therefore possible that our subgroup of patients 65 to 70 years of age was enriched with patients who were more likely to have worse outcomes.”

Finally, there were 165 patients with methylated O6-methylguanine–DNA methyltransferase (MGMT) status. Among these patients, the median overall survival was 13.5 months with temozolomide compared with 7.7 months in patients assigned radiotherapy alone (HR, 0.53; 95% CI, 0.38–0.73; P < .001). No significant benefit was observed in the 189 patients with unmethylated MGMT status; the median overall survival was 10 months with radiotherapy plus temozolomide compared with 7.9 months for radiotherapy alone (P = .055).

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