Valproic Acid: A Happy Accident, Again?
A recent study suggested that patients with glioblastoma treated with radiation and temozolomide lived a few months longer if they were taking valproic acid for seizure control rather than an enzyme-inducing antiepileptic drug (AED) or no AED at all.
All of the patients had newly diagnosed glioblastoma and participated in a large randomized clinical trial of initial radiotherapy or radiotherapy with adjuvant temozolomide chemotherapy. Overall survival was 17.35 months in patients on valproic acid (n = 49), 14.42 months on an enzyme-inducing AED (n = 113), and 13.96 months on no AED (n = 103). Benefits in the valproic acid group could not be explained by an increased number of patients with the O methylguanine-DNA methyltransferase gene, which is associated with better response to temozolomide.
Could it be? Has valproate been discovered by accident as an antibrain tumor drug?
If so, it would be at least the second time that valproic acid has accidentally been discovered as a useful drug for neurologic disease. In 1962, Pierre Eymard observed that valproic acid had potent anticonvulsant properties while using it as an organic solvent in rat epilepsy experiments. Valproic acid has a broad spectrum of activity and is now widely used for both partial and generalized seizures.
Or could it be the third time, because headache specialists noted that valproic acid could prevent migraines?
Or the fourth, because psychiatrists found that it also acts as a mood stabilizer in bipolar disorder?
Glioblastoma multiforme has proven remarkably resistant to effective therapy, despite decades of oncologic research. The clinical course of my most recent patient with glioblastoma multiforme, an active businesswoman and mother in her 40s, was typically discouraging. She presented with partial seizures (initially believed to be panic attacks until she had a full-blown convulsion on her living room couch). Over the next few months, her seizures were well controlled with levetiracetam. However, despite aggressive medical and surgical therapy for her brain tumor, she was dead within 6 months.
Valproic Acid: A Happy Accident, Again?
A recent study suggested that patients with glioblastoma treated with radiation and temozolomide lived a few months longer if they were taking valproic acid for seizure control rather than an enzyme-inducing antiepileptic drug (AED) or no AED at all.
All of the patients had newly diagnosed glioblastoma and participated in a large randomized clinical trial of initial radiotherapy or radiotherapy with adjuvant temozolomide chemotherapy. Overall survival was 17.35 months in patients on valproic acid (n = 49), 14.42 months on an enzyme-inducing AED (n = 113), and 13.96 months on no AED (n = 103). Benefits in the valproic acid group could not be explained by an increased number of patients with the O methylguanine-DNA methyltransferase gene, which is associated with better response to temozolomide.
An Abundance of Serendipity
Could it be? Has valproate been discovered by accident as an antibrain tumor drug?
If so, it would be at least the second time that valproic acid has accidentally been discovered as a useful drug for neurologic disease. In 1962, Pierre Eymard observed that valproic acid had potent anticonvulsant properties while using it as an organic solvent in rat epilepsy experiments. Valproic acid has a broad spectrum of activity and is now widely used for both partial and generalized seizures.
Or could it be the third time, because headache specialists noted that valproic acid could prevent migraines?
Or the fourth, because psychiatrists found that it also acts as a mood stabilizer in bipolar disorder?
A Devastating Disease
Glioblastoma multiforme has proven remarkably resistant to effective therapy, despite decades of oncologic research. The clinical course of my most recent patient with glioblastoma multiforme, an active businesswoman and mother in her 40s, was typically discouraging. She presented with partial seizures (initially believed to be panic attacks until she had a full-blown convulsion on her living room couch). Over the next few months, her seizures were well controlled with levetiracetam. However, despite aggressive medical and surgical therapy for her brain tumor, she was dead within 6 months.
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