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.