Perioperative Chemotherapy With Cisplatin (Cp) And Doxorubicin (Dox) With And Without High-Dose Methotrexate (Hdm) In Adult Osteosarcoma (Aot): Is Methotrexate Warranted?

10523 Background: treatment of AOT consists of perioperative chemotherapy and surgical resection. Standard chemotherapy in AOT consists of CP and DOX. Although considered standard of care in the pediatric population, the use of HDM remains controversial in adults. In addition, it is associated with greater toxicity rates, leading many specialized centers to drop it. This study aims to review treatment efficacy in localized AOT treated at our institution to ascertain the role of HDM in this disease. Methods: this retrospective study included consecutive patients with localized AOT treated at the Instituto do Cancer do Estado de São Paulo (ICESP) from 2008 to 2014 that received at least one perioperative chemotherapy cycle. Chemotherapy regimens consisted of DOX and CP (group 1). A subgroup of patients also received HDM (group 2). Analysis of overall survival (OS), disease free survival (DFS) and treatment toxicities were performed. Results: final analysis included 26 patients, 16 treated in group 1 and 10 in group 2. Most patients presented ECOG performance status 0-2 (93.8 and 80%) and lower extremity primary tumours (62.5 and 80.0%), for group 1 and group 2 respectively. Despite lower average age (35.0±12.1 and 18.9±2.1 y), group 2 presented more grade (G) 3/4 thrombocytopenia (0 and 15.8%) and G3/4 mucositis (0 and 21.1%), while group 1 presented more neutropenia G3/4 (46.6 and 26.3%). Both groups presented no G3/4 renal toxicities. Two grade 5 toxicities occurred in group 2 (bleeding and neutropenia), both after the first HDM cycle. Efficacy analysis revealed no difference in DFS (4.38±0.61 and 2.3±0.54y, p = 0.228) and OS between groups (4.70±0.56 and 2.52±0.57y, p = 0.107), with a trend to better outcomes in group 1. The 4-year OS was 65.6 and 32.8% for group 1 and 2 respectively. Conclusions: HDM chemotherapy was associated with greater severe and lethal toxicity when added to CP and DOX perioperative chemotherapy in AOT. In addition, it does not seem to impact on efficacy. This data does not support the use of HDM in the treatment of AOT.