Glioblastoma Treatment with Temozolomide and Bevacizumab and Overall Survival in a Rural Tertiary Healthcare Practice

Abstract

Background: The efficacy of temozolomide (TMZ) chemotherapy for treating newly diagnosed glioblastoma (GBM), a primary brain tumor with short survival, was demonstrated in a clinical trial in 2005, and since then, the standard-of-care for newly diagnosed GBM has been maximal safe surgery followed by 60 Gray of radiation with concomitant and adjuvant TMZ (standard radiotherapy and TMZ). In 2009, clinical trials also reported on the efficacy of bevacizumab for treating recurrent GBM. We performed a retrospective cohort study to evaluate the impact of treatment regimens on overall survival for patients with GBM at a rural tertiary healthcare practice.

Methods: We retrospectively reviewed the medical records of 307 consecutive, newly diagnosed GBM patients at one institution between 1995 and 2012 and assessed treatment patterns. We also compared overall survival according to the treatment received.

Results: Only 0.6% (1/163) of patients diagnosed before 2005 received standard radiotherapy and TMZ versus 36.1% (52/144) of patients diagnosed since 2005 (P < 0.0001). For patients who received standard radiotherapy and TMZ, the median overall survival was 17.0 months versus 7.0 months for patients who received 60 Gray of radiation but no chemotherapy (P = 0.0000078). The median overall survival was 15.4 months in the 19 patients treated with bevacizumab monotherapy at first GBM recurrence versus 6.8 months in the 32 patients with no treatment at first GBM recurrence (P = 0.00015), but patients who received bevacizumab were younger and more likely to have had a surgical resection and 60 Gray of radiation at diagnosis.

Conclusions: TMZ and bevacizumab therapies were rapidly adopted in a rural tertiary healthcare setting, and patients who received these treatments had increased overall survival. However, advantageous prognostic factors in patients who received bevacizumab at recurrence may have influenced the extent of the increase in overall survival attributed to this treatment.

Figure 1

Overall survival according to bevacizumab treatment at first glioblastoma recurrence. Sample sizes were n = 24 for patients who received bevacizumab and other agents (BVZ and other), n = 19 for patients who received bevacizumab alone (BVZ alone), n = 22 for patients who received only non-bevacizumab treatment (Other), and n = 32 for patients who received no treatment (None). The distance spanned by the bottom and top of each box represents the interquartile range, the enclosed line represents the 50^th percentile, and the whiskers stretch to the data point that is not > 1.5 times the interquartile range from the box. Data points that fell outside the range of the whiskers were represented by small, open circles. ^∗P = 0.0000033 and ^∗∗P = 0.00015 for paired comparisons between treatment groups using Wilcoxon rank sum test. Abbreviation: BVZ, bevacizumab.