title: Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.
abstract: Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.
authors.affiliation: Neuro-Oncology Unit, Hospital Universitari de Bellvitge and ICO Duran i Reynals, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), C/Feixa Llarga s/n, 08907, L'Hospitalet del Llobregat, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Simó
authors.forename: Roser
authors.initials: R
authors.lastname: Velasco
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.forename: Eugenia
authors.initials: E
authors.lastname: Verger
authors.forename: Miguel
authors.initials: M
authors.lastname: Gil
authors.forename: Estela
authors.initials: E
authors.lastname: Pineda
authors.forename: Jaume
authors.initials: J
authors.lastname: Blasco
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruna
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality; D059248:Chemoradiotherapy / Q000009:adverse effects*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide