Avoiding glucocorticoid administration in a neurooncological case

Abstract

KEY WORDSglioblastoma, celecoxib, dexamethasone, cerebrospinal, blood brain barrier, temozolomide ABBREVIATIONS GC glucocorticoid GBM glioblastoma multiforme WHO Grade IV CSF cerebrospinal fluid ACKNOWLEDGEMENTSWe thank Ingrid Herr for valuable suggestions. Clinical Case ReportAvoiding Glucocorticoid Administration in a Neurooncological Case ABSTRACTRestricting glucocorticoid (GC) use in the treatment of patients with a solid tumor may help improving outcome. Here, we report administration of celecoxib rather than dexamethasone to prevent brain edema in a patient with a cerebellar glioblastoma multiforme WHO grade IV (GBM) upon the patient's request, as well as determining cerebrospinal fluid (CSF) and serum concentrations. CSF concentration (0.04 µM) was 54 times below serum concentration (2.18 µM), or 2500 times below levels inhibiting GBM cells in vitro (100 µM), revealing a blood CSF barrier for celecoxib. The patient did not require dexamethasone for the entire treatment. GC administration hence was avoided successfully in this case. The role of COX-2 inhibitors in treatment of GBM is detailed, leading to the conclusion of a pressing need for a clinical evaluation of non-steroidal COX-2 inhibitors with the ability to penetrate into brain tumors.

Influence of Caloric Restriction on Constitutive Expression of NF-κB in an Experimental Mouse Astrocytoma

“…Although the glucocorticoid, dexamethasone, is currently the standard drug of choice for attempting to mitigate tumor-associated inflammation and edema [14], [15], [16] the drug has been found to produce a significant number of adverse effects including hyperglycemia—which may ultimately facilitate tumor growth, gastritis, gastrointestinal bleeding, weight-gain, Cushing's syndrome, and immuno-suppression [15] [16] [17], [18]. In light of the aforementioned, less toxic therapies are necessary to manage peri-tumoral inflammation and the sequelae of tumor cell infiltration and accompanying cerebral edema in patients with malignant astrocytoma.…”

Potential interactions of prescription and over‐the‐counter medications having antioxidant capabilities with radiation and chemotherapy

“…All glucocorticoids need to be utilized with the understanding of caution and employed conservatively along with chemotherapy and radiation whenever possible. Alternate strategies should be encouraged . For example, Zhang et al .…”

Corticorelin acetate injections for the treatment of peritumoral brain edema

“…Thus the use of mannitol is restricted to treating inpatients typically presenting with an acute, gross exacerbation of PBE in which impending herniation is of serious concern. Nonsteroidal agents, including indomethacin, ibuprofen, boswellic acid and selective COX-2 inhibitors (celecoxib), have also been considered for treatment of PBE in patients with brain tumors [51]. Celecoxib, in particular, has led to the reduction of brain edema in experimental models of brain bleeding [51,52].…”

“…Nonsteroidal agents, including indomethacin, ibuprofen, boswellic acid and selective COX-2 inhibitors (celecoxib), have also been considered for treatment of PBE in patients with brain tumors [51]. Celecoxib, in particular, has led to the reduction of brain edema in experimental models of brain bleeding [51,52]. The antineoplastic effects of celecoxib, including radiosensitization, inhibition of angiogenesis and induction of apoptosis and immune response in tumor cells, are well established and have thus been the focus of investigational study of this drug.…”

“…Additional studies highlighting its specific effect on PBE, while sparing corticosteroid use, are necessary. However, other COX-2 inhibitors, namely rofecoxib and valdecoxib, have been taken off the market due to associated cardiovascular risks [51].…”