A retrospective safety analysis of adult patients treated with high-dose methotrexate for osteosarcoma in Stockholm, Sweden.

Abstract

10083 Background: Patients with osteosarcoma are routinely treated with pre- and post-operative chemotherapy that includes high-dose methotrexate. The treatment is associated with a risk of severe renal and hepatic toxicity. Methods: All patients with osteosarcoma that had received at least one cycle of high-dose methotrexate at the adult oncology department, Karolinska University Hospital were retrospectively identified. Treatment toxicity, including hematologic, renal, hepatic toxicity, infections and oral mucositis were registered and graded according to CTCAE v 4.0. A possible relationship between methotrexate blood concentration and toxicity was investigated. Results: Sixteen eligible patients that had received a total of 103 cycles of high-dose methotrexate were identified. Ten patients experienced a severe hepatic toxicity, (Grade 3, n=5 and Grade 4, n=5). Grade 3 renal toxicity was seen in one patient and although reversible, it led to treatment interruption. Reversible, grade 2 elavation of serum creatinine occured in 5 cases. Four grade 3 infections were seen in 2 patients and 8 patients had at least one occurrence of Grade 3 oral mucositis. Thrombocytopenia was a common event (Grade 3, n=5 and Grade 4, n=2) but no severe bleeding complications were observed. One patient died as a result of multi-organ failure two days after methotrexate administration. Methotrexate blood concentration at 24 hours from administration could predict for renal toxicity (p<0.005, by chi-square test), but not for other toxicity. Conclusions: High-dose methotrexate in adult patients with osteosarcoma was frequently associated with severe, however reversible toxicity.