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07-09-2011 | General practice | Article

Valproic acid may enhance survival in glioblastoma patients


Free abstract

MedWire News: The type of antiepileptic drug (AED) given to patients undergoing treatment for glioblastoma may affect their survival, study results suggest.

The findings arise from an analysis of data from a clinical trial database of 573 patients who underwent radiotherapy with or without temozolomide (TMZ) for newly diagnosed glioblastoma.

"Despite the limitations of this retrospective analysis, these results suggest that the choice of AED in patients with brain tumors should be carefully considered because it may affect survival," say Michael Weller (University Hospital Zurich, Switzerland) and colleagues.

"The present observation also further supports a recent trend to favor a non-enzyme-inducing (EI) AED (EIAED) for patients with a malignancy to allow administration of modern chemotherapy and targeted agents that often show increased hepatic metabolism if patients are given an EIAED."

The researchers conducted their study following reports that use of an EIAED could improve outcome in glioblastoma patients. But their study, which appears in the journal Neurology, found the reverse effect.

On starting treatment, 30.5% of patients were not taking an AED, 48.3% were taking an EIAED, and 23.4% were taking a non-EIAED, which was valproic acid in all but two cases.

Overall survival was similar in patients taking valproic acid, an EIAED only, and no AED, at respective medians of 12.78, 13.19, and 12.52 months. But among patients receiving radiotherapy plus TMZ, those taking valproic acid had a longer median survival, of 17.35 months compared with 14.42 and 13.96 months in patients taking an EIAED and no AED, respectively.

Patients taking no AED had a 33% survival benefit with adjuvant TMZ versus radiotherapy alone and those taking an EIAED had a 31% survival benefit. But patients taking valproic acid had a significantly larger 61% survival benefit with adjuvant TMZ, after accounting for major prognostic factors, including age, extent of surgery, corticosteroid administration, and Mini-Mental State Examination results.

There was a significant interaction for the effect of valproic acid versus an EIAED on treatment-related survival.

In an accompanying editorial, Patrick Wen (Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA) and David Schiff (University of Virginia Medical Center, Charlottesville, USA) said: "While the results of this study are intriguing, they should be interpreted with caution and additional information is required."

They noted that survival among patients receiving radiotherapy alone was slightly worse with valproic acid than with EIAEDs and no AED, at 10.09, 12.48, and 11.96 months, respectively, which "raises the possibility that the apparent benefit of valproic acid with radiation and [TMZ] occurred by chance."

The editorialists observed that analysis of other, ongoing studies may confirm or refute the findings. "Until data from these studies become available, it is unclear whether the potential survival benefit of valproic acid outweighs the definite increase in hematologic toxicity," they concluded.

By Eleanor McDermid

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