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Hypofractionated radiation, temozolomide effective in elderly patients with glioblastoma
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Hypofractionated radiotherapy or temozolomide monotherapy may be a viable treatment option for elderly patients with glioblastoma multiforme, according to results of a systematic literature review.
Patients with MGMT promotor methylation may experience a greater benefit from temozolomide (Temodar, Merck Sharp Dohme) than from the short-course radiotherapy, results also showed.
Sunit Das
Sunit Das, MD, PhD, professor of neurosurgery at the University of Toronto, and colleagues sought to evaluate the optimal therapeutic approach for elderly patients with glioblastoma multiforme. Although the standard of care for the disease shifted due to studies evaluating temozolomide chemotherapy combined with radiotherapy, only a small number of patients enrolled on these studies were aged 65 years or older.
“Elderly patients constitute an expanding proportion of cases of newly diagnosed glioblastoma,” Das told HemOnc Today. “The treatment of elderly patients with glioblastoma remains challenging, as these patients often do not have the physiologic reserve necessary to tolerate aggressive surgery and standard chemoradiation. Our goal with this work was to construct an intellectual foundation that could inform clinicians in their treatment recommendations for elderly patients with glioblastoma.”
Das and colleagues conducted a review of 185 articles published between 2005 and 2013, of which 23 were included in the final analysis. Three of these studies reported OS in elderly patients who were treated with temozolomide alone and six studies reported OS in elderly patients treated with radiotherapy alone. There were only two randomized trials — the NOA-08 and Nordic trials — that compared radiation with temozolomide monotherapy in patients aged 65 years or older.
Trial results
The NOA-08 trial — which compared 100 mg/m² temozolomide every other week with standard radiotherapy (60 Gy in 30 fractions) — concluded temozolomide alone was not inferior to radiotherapy alone. Median OS in the temozolomide arm was 8.6 months compared with 9.6 months in the radiotherapy arm (P = .03). Further, MGMT promotor methylation was associated with longer EFS in the temozolomide group compared with the radiotherapy group (8.4 vs. 4.6 months).
Researchers of the Nordic trial randomly assigned patients to one of three treatment arms: standard-dose temozolomide (200 mg/m² on days 1-5 of a 28-day cycle for 6 cycles), standard radiotherapy (60 Gy in 30 fractions), or hypofractionated radiotherapy (34 Gy in 10 fractions).
Results of this analysis indicated the median OS was significantly longer in the temozolomide arm (8.3 months) and the hypofractionated radiotherapy arm (7.5 months) than in the standard radiotherapy arm (6 months). In the temozolomide group, MGMT promotor methylation was associated with a higher survival rate than unmethylated MGMT (9.7 vs. 6.8 months).
Das and colleagues also evaluated data from the randomized ANOCEF trial, which evaluated the addition of radiotherapy to supportive treatment in patients aged 70 years or older. Results showed median OS for patients who received supportive care plus radiotherapy was 6.7 months, which was superior to supportive care alone (3.9 months).
The randomized EORTC-NCIC trial compared standard radiotherapy vs. chemoradiation plus temozolomide for patients with glioblastoma multiforme who were aged up to 70 years. Results showed patients aged older than 60 years had better OS with radiation alone than with chemoradiation (11.8 months vs. 10.9 months).
In a secondary analysis of patients aged older than 70 years in a non-randomized trial, MGMT promotor methylation was associated with improved OS compared with unmethylated MGMT (8.4 vs. 6.4 months). An additional, non-randomized, population-based analysis indicated median OS in patients aged older than 70 years who received radiotherapy alone was 7.4 months. The addition of adjuvant chemotherapy to temozolomide resulted in a notable survival advantage (median, 13.4 months; 95% CI, 10.2-19.2).
Implications
Overall, Das and colleagues noted their literature review revealed a lack of randomized clinical studies that compare temozolomide vs. radiotherapy in elderly patients with glioblastoma. They also noted that studies tended to vary in their definition of “elderly” and that treatment paradigms were not consistent across studies.
Still, the literature supports the use of hypofractionated radiotherapy or temozolomide monotherapy for elderly patients with glioblastoma multiforme. The use of temozolomide is especially warranted in patients with MGMT promoter methylation, researchers wrote.
“We concluded that radiation therapy alone or temozolomide monotherapy, particularly in patients with tumors in which the MGMT gene is methylated, are reasonable choices for treatment in this population,” Das said. “We also found that standard therapy with surgical resection and adjuvant chemoradiation with temozolomide remains the treatment of choice in elderly patients who are capable of tolerating these stressors.” – by Anthony SanFilippo
For more information:
Sunit Das, MD, PhD, can be reached at the University of Toronto, 563 Spadina Crescent, Toronto, ON, M57 2J7; email: sunit.das@utoronto.ca.
Disclosure: The researchers report no relevant financial disclosures.
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