Perioperative chemotherapy with and without high-dose methotrexate in adult osteosarcoma.

Treatment of adult osteosarcoma (AOS) includes perioperative chemotherapy and surgery. Standard chemotherapy consists of cisplatin (CP) and doxorubicin (DOX). Although considered the standard of care for pediatric patients, high-dose methotrexate (HDM) remains controversial in adults. We aimed to evaluate the role of HDM in AOS treated with curative intent. This study included patients with AOS who received perioperative chemotherapy with DOX and CP (group 1; N=16) and DOX, CP, and HDM (group 2; N=10). The primary endpoint was grade 3 or superior toxicities. The secondary endpoints included overall survival (OS) and disease-free survival. Despite lower average age (35.0±12.1 vs. 18.9±2.1 years), group 2 presented more grade 3-4 thrombocytopenia (0 vs 50%) and mucositis (0 vs 40%), whereas group 1 presented more grade 3-4 neutropenia (43.75 vs 40%). No grade 3-4 renal toxicities occurred. Two grade 5 toxicities occurred in group 2, both after the first HDM cycle. Disease-free survival (4.38±0.61 vs. 2.3±0.54 years, P=0.228) and OS (4.70±0.56 vs 2.52±0.57 years, P=0.107) were not statistically different, but presented a trend toward better outcomes in group 1. The 4-year OS was 65.6 and 32.8% for groups 1 and 2, respectively. In conclusion, HDM was associated with greater severe and lethal toxicity when added to CP and DOX in AOS. Also, it does not seem to impact on treatment efficacy. These data do not support the use of HDM for the perioperative treatment of AOS.

Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus?

The role of antiepileptic drugs (AED) prophylaxis in primary brain tumor (PBT) seizure-naïve patients remains unclear. Additionally, AED are associated with severe side effects, negative impact on cognition and drug interactions. Little is known about current practice regarding prophylactic AED use in PBT. We investigated its use in a tertiary care cancer center. We reviewed medical records of 260 patients registered in our center between 2008 and 2012, focusing on prophylactic AED use. A descriptive analysis was performed with SPSS IBM version 20.0. Median age was 44.5 years (11-83). Most patients had ECOG PS ≤1 (76.4 %). Among 141 seizure-naïve patients, 70.2 % received an AED as primary prophylaxis (PP). Most commonly used drugs as PP were phenytoin (85.9 %), carbamazepine (6.1 %) and phenobarbital (5.1 %). In only 14 patients (14.1 %) AEDs were eventually discontinued, in a median time of 5.9 months (1.1-76.8 m). AED were used as PP in 60 % of low-grade gliomas, 73.3 % of anaplastic gliomas and 93.9 % of glioblastoma patients. Twenty-seven patients (27.3 %) on PP presented seizures, generally associated with tumor progression. Of the 42 seizure-naïve patients not receiving AED prophylaxis, only two presented seizures, which occurred during or within the first week post-radiotherapy. In this cross-sectional study, prophylactic AED use in PBT was extremely high. Postoperatively, AED were discontinued in a minority of patients, mostly after a prolonged period. Current prophylactic AED use patterns in PBT are not in accordance with established guidelines.