Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

Abstract

Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas

“…A clear relationship between the studied variables and therapeutic outcome is difficult to establish, considering the multitude of other factors, such as protein binding, membrane transport, dihydrofolate reductase levels, tissue distribution, or concurrent drugs, which may also influence the efficacy of MTX. Nevertheless, as has been reported for other malignancies (Evans et al, 1986;Graf et al, 1994;Delepine et al, 1995;Bacci et al, 1998), the characterisation of the MTX variables investigated could be useful to identify different risk groups and to define the optimal administration schedule of this drug in PCNSL patients. HD-MTX is the most effective drug against PCNSL; any regimen without this drug is associated with outcomes which are no better than with RT alone (Schultz et al, 1996;O'Neill et al, 1999;Mead et al, 2000).…”

“…A single study comparing some MTX parameters in PCNSL patients treated with blood -brain barrier disruption or with systemic chemotherapy has been reported (Zylber-Katz et al, 2000), but their impact on outcome has not been analysed. Conversely, the prognostic role of MTX pharmacokinetics has been reported in other malignancies in which this drug plays a critical role, such as acute leukaemia (Evans et al, 1986) and osteosarcoma (Graf et al, 1994;Delepine et al, 1995;Bacci et al, 1998). Patients with acute leukaemia have been grouped according to a slow, medium or fast CL MTX , obtaining an inverse association with outcome (Evans et al, 1986).…”

“…In spite of its central role in PCNSL treatment, the optimal dose, administration schedule, and dose timing of MTX have not been clearly defined. Moreover, contrary to what is observed in other malignancies in which MTX plays a crucial role, such as acute leukaemia (Evans et al, 1986) and osteosarcoma (Graf et al, 1994;Delepine et al, 1995;Bacci et al, 1998), where a significant association between MTX parameters and outcome has been reported, the impact on toxicity and outcome of MTX administration schedule has not been investigated in PCNSL.The analysis of some MTX parameters, such as the area under the curve (AUC MTX ), dose, dose intensity (DI MTX ), and infusion rate (IR MTX ), as well as the plasmatic creatinine clearance (CL crea ) could allow us to identify subgroups of patients with increased risk of severe toxicity or disappointing outcome, as well as to define the optimal MTX administration schedule against PCNSL. This paper reports the analysis of the impact on toxicity and outcome of the above-mentioned variables in a retrospective multicentre series of 45 immunocompetent patients with PCNSL treated with HD-MTXbased primary chemotherapy.…”

“…In spite of its central role in PCNSL treatment, the optimal dose, administration schedule, and dose timing of MTX have not been clearly defined. Moreover, contrary to what is observed in other malignancies in which MTX plays a crucial role, such as acute leukaemia (Evans et al, 1986) and osteosarcoma (Graf et al, 1994;Delepine et al, 1995;Bacci et al, 1998), where a significant association between MTX parameters and outcome has been reported, the impact on toxicity and outcome of MTX administration schedule has not been investigated in PCNSL.…”

Global Protein-expression Analysis of Bone and Soft Tissue Sarcomas

“…Over the last decade, considerable efforts have been made for this purpose. Not only classic parameters such as histologic subtype, tumor location, and presence of metastatic disease at diagnosis [1], but also several molecules related to drug metabolism/ transport or tumor development have been reported to correlate with the chemosensitivity of osteosarcoma [3,15,17,23].…”