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Retrospective study of feasibility of high-dose methotrexate in adult osteosarcoma patients over 40 years.

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2016.34.15_suppl.e22509

1527-7755

Nadia Hindi, Alejandro Falcón, Roberto Lasso, Maria Pilar Sancho Marquez, Inmaculada Sanchez-Simon, Ana Fernández‐Teijeiro, Catalina Márquez-Vega, M. Noguer, Javier Martín‐Broto,

Polyomavirus and related diseases

e22509 Background: High-dose methotrexate (HDMTX) is a backbone of systemic therapy of osteosarcoma along with cisplatin and doxorubicin. Children excrete MTX more effectively than adults and on this basis most protocols exclude HDMTX in patients (pts) aged over 40 years. Folinic rescue, hydration and plasma drug concentration are critical in the HDMTX management. Here we review our experience with HDMTX in a series of pts > 40y Methods: Those osteosarcoma pts treated in our institution with chemotherapy containing HDMTX (12g/m2), since July 2006 to October 2015 were reviewed. Data regarding clinicopathologic characteristics, therapy, toxicity, and survival were collected. Kaplan-Meier method was used for overall survival (OS) and relapse free survival (RFS) analysis Results: 18 pts were identified: M/F 9/9; median age 51y (41-63), localized disease in 14 (78%) and metastatic in 4 (22%). Median total dose per patient of MTX was 50 mg/m2. Neoadjuvant HDMTX was given at a dose intensity (DI) of 3.5 g (2.2-5.3)/m2/week, whereas in adjuvant phase, HDMTX was administered at 2.5 g (1.4-8.0)/m2/week. This represents 112% and 78% of planned DI in pre and postoperative phase respectively. Regarding G > 3/4 toxicity,10 pts (56%) had febrile neutropenia, 3 pts (17%) thrombopenia and 6 pts (33%) anemia, all related with anthracycline/platinum administration. With regard to MTX-related toxicity, 5 pts (28%) had G3-4 transaminitis (ALT). Delayed MTX-excretion was reported in 14 pts (78%). Creatinine levels did not significantly vary after HDMTX administration. In those pts receiving neoadjuvant HDMTX median necrosis on surgical specimen was 50% (0-100), with 27% of pts achieving good pathological response (pR) (necrosis > 90%). 66% of pts with poor pR relapsed and no pts achieving a good pR have relapsed. In pts with localized disease, 5-y RFS rate was 53.8%, and 6 pts (43%) relapsed at the time of this analysis. Globally, 4 pts (28.5%) have died, resulting in an actuarial 5-y OS of 70% Conclusions: HDMTX in pts with osteosarcoma > 40y is feasible with a good dose intensity. Although delayed excretion was more frequent than reported in younger patients, toxicity profile reproduced data from previous reports on children and adolescents