Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma. Analysis of the literature.

Abstract

The authors surveyed the published clinical trial literature on the subject of localized high grade osteosarcoma in order to develop new hypotheses dealing with drug-dose combinations in the treatment of this disease. A computerized literature search was conducted to identify all available published reports of the clinical trials using high dose methotrexate (MTX) in multidrug protocols treating osteosarcoma. Thirty studies, including discussion of high dose MTX (> 7.5 g/m2 per course) and precise quantification of 5-year disease free survival (DFS), fulfilled the inclusion criteria of this dose-intensity analysis. The total number of patients treated in eligible studies was 1909. Correlation among the planned total doses, the dose intensities of the drugs, and the 5-year DFS were tested by regression analysis. No correlation of any other drug dose or dose intensity with DFS appeared as important as the MTX finding. In multivariate analysis, the dose intensity of MTX was found to be the one most correlated with DFS. This correlation appeared to hold for adjuvant and neoadjuvant trials. The dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localized high grade osteosarcoma.