Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells

Abstract

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

5-ALA–induced fluorescence as a marker for diagnostic tissue in stereotactic biopsies of intracranial lymphomas: experience in 41 patients

“…A recent in vitro study of glioblastoma cells demonstrated that corticosteroids result in a significantly decreased 5-ALA-induced PpIX production by tumor cells. 13 Additionally, we hypothesized that immunosuppression might alter the presence of fluorescence in lymphomas. Thus, we also investigated the influence of prior treatment with corticosteroids or immunosuppression on fluorescence.…”

Intraoperative fluorescence diagnostics in surgery of intracranial meningiomas: analysis of 101 cases

“…J. Lawrence и соавт. [38] показали, что дексаметазон (как сам по себе, так и в сочетании с фенитоином и вальпроатами) снижает накопление ПП IX в клетках культуры глиомы. Это послужило основанием для изучения влияния противосудорожных препаратов на флуоресцирующий эффект в нашей когорте пациентов с менингиомами.…”

Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen

“…Dexamethasone, desipramine, levetiracetam, phenytoin, and valproic acid are drugs that tend to diminish GB fluorescence after 5-ALA so might be best avoided during 5-ALA PDT and CAALA [55,56]. Also potential generators of increased nitric oxide tend to antagonize 5-ALA [57] and so should be avoided.…”