Methotrexate for high-grade osteosarcoma in children and young adults

Abstract

Since no RCTs or CCTs in which only the use of MTX differed between the treatment groups were identified, no definitive conclusions can be made about the effects on antitumour efficacy, toxicities and quality of life of the addition of MTX to treatment of children and young adults with primary high-grade osteosarcoma. The same is true for combinations of treatment including and not including MTX other than treatment with MTX versus treatment with cisplatin. Only 1 RCT comparing MTX with cisplatin treatment was available and therefore, no definitive conclusions can be made about the effectiveness of these agents in children and young adults with primary high-grade osteosarcoma. Furthermore, this study was performed in a different treatment era. Nowadays single agent treatment of osteosarcoma is considered inadequate. Based on the currently available evidence, we are not able to give recommendations for the use of MTX in clinical practice. More high quality research is needed.

Comparative Outcome of Thai Pediatric Osteosarcoma Treated with Two Protocols: the Role of High-Dose Methotrexate (HDMTX) in a Single Institute Experience

“…The effective chemotherapeutic agents against osteosarcoma are CDDP (Ochs et al, 1978;Baum et al, 1979), CBDCA (Choeyprasert et al, 2014), ADR (Cores et al, 1972;Choeyprasert et al, 2014) and IFO (Harris et al, 1995;Harris et al, 1998) and HDMTX (Jaffe et al, 1983;Rosen G, 1993;Delepine et al, 1996;Goorin et al, 2003;Lewis et al, 2007). Recently, HDMTX seems to be one of the most active agents against osteosarcoma; however, there is still no consensus on a standard chemotherapy approach, including even the HDMTX-based protocol (Jaffe et al, 1985;van Dalen et al, 2011).…”

“…Since then, several schemes of multiagent adjuvant chemotherapy have been assessed, but recent meta-analysis had still shown no consensus in the addition of HDMTX to treatment of pediatric osteosarcoma. This lack of consensus results from the lack of an appropriate randomized-and case-controlled trial comparing the anti-tumor efficacy of HDMTX between treatment groups (Van Dalen et al, 2011). The purpose of this retrospective study was to assess the therapeutic efficacy in two consecutive eras in order to demonstrate the role of HDMTX-containing chemotherapeutic protocol (MTX(+) protocol) in the treatment of pediatric osteosarcoma at our university hospital.…”

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

“…Rankings based on simulationsHR hazard ratio, OR odds ratio, 95% CrI 95% credible intervals, RBC red blood cell, PLT platelet, G-CSF granulocyte colony-stimulating factor, DC doxorubicin + cisplatin, MDC methotrexate + doxorubicin + cisplatin, MDCI methotrexate + doxorubicin + cisplatin + ifosfamide of osteosarcoma patients, it should be recognized the serious adverse effects[39]. According to our results, that MDCI was associated with a greater total severe AEs than DC [MDCI: OR = 4.69, 95% CrI (2.79, 7.87)].…”

Perspectives of the Role of Chemotherapy in the Management of Osteosarcoma

“…Unlike any other agent it is the only drug that has been subjected to a randomized trial to test its efficacy against an effective agent. This communication constituted the basis of a Cochrane review on MTX and osteosarcoma [65]. It was shown to be inferior to intra-arterial CDP in the treatment of the primary tumor [66].…”