Radioimmunotherapy and Temozolomide in the Treatment of Glioblastoma Multiforme: A 20 Year Experience

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Appendix. Supplementary data
• Copyright

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Purpose/Objective(s) 

The standard treatment of patients (pts) with glioblastoma multiforme (GBM) is surgery and radiation therapy (XRT) ± chemotherapy. Recently, temozolomide (TMZ) has been shown to offer a survival benefit. Adjuvant radioimmunotherapy with ¹²⁵I-labeled anti-epidermal growth factor receptor monoclonal antibody 425 (¹²⁵I-EGFR MAb 425) may also increase survival. In a phase II clinical study, we compared the survival of 3 treatment groups: surgery+XRT (CTL), ¹²⁵I-EGFR MAb 425+surgery+XRT (RIT), and TMZ+¹²⁵I-EGFR MAb 425+surgery+XRT (TMZ+RIT).

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Materials/Methods 

Pts with newly diagnosed and histologically proven GBM were eligible. Postoperative XRT was give to a median dose of 60 Gy following debulking surgery. ¹²⁵I-EGFR MAb 425 was given by 3 weekly intravenous injections of 1.8 GBq of ¹²⁵I-EGFR MAb 425 following surgery and XRT. TMZ was given concomitantly (75 mg/m²/d, 35–42d) with XRT followed by 6 cycles of adjuvant TMZ (150–200 mg/m²/d × 5d, q28d). Median survival was the primary endpoint.

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Results 

From 1988 to 2007, 273 GBM pts were treated at Hahnemann University Hospital: CTL (n = 81), RIT (n = 132), and TMZ+RIT (n = 60). Median age in years for CTL, RIT, and TMZ+RIT group was 66.0, 52.5, and 53.5, respectively (p < 0.001). The percentage of pts who received debulking surgery for CTL, RIT, and TMZ+RIT group was 70.4, 74.2, and 86.7, respectively (p = NS). The percentage of pts who received XRT in CTL, RIT, and TMZ+RIT group was 67.9, 98.5, and 100, respectively (p < 0.001). Pts who did not receive both surgery+XRT were excluded from median survival calculations. Median survival in months overall (n = 187), CTL (n = 39), RIT (n = 97), and TMZ+RIT (n = 51) group was 14.0, 10.2, 14.5, and 20.4, respectively. Log rank analysis resulted in RIT vs CTL, p < 0.001, TMZ+RIT vs CTL, p < 0.001, and TMZ+RIT vs RIT, p = 0.011. On multivariate analysis (proportional hazards) using all 273 pts controlling for age, surgery, and XRT, the hazard ratio for RIT vs CTL, TMZ+RIT vs CTL, and TMZ+RIT vs RIT was 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively (Table 1).

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Conclusions 

Historical control pts differ from both treatment groups being older in age and less likely to receive or complete XRT. However, after controlling for these factors, the differences in median survival between each of the treatment groups and control remain statistically significant. Treatment with ¹²⁵I-EGFR MAb 425 confers survival benefits over controls. Combination ¹²⁵I-EGFR MAb 425+TMZ provides the greatest survival benefit. This study represents the largest reported series using radioimmunotherapy in the treatment of GBM.

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Appendix. Supplementary data 

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Appendix. Supplementary data 

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ijrobp.2007.07.088