INFLUENCE OF METHOTREXATE DOSE INTENSITY ON OUTCOME OF PATIENTS WITH HIGH-GRADE OSTEOGENIC OSTEOSARCOMA - ANALYSIS OF THE LITERATURE

BACKGROUND. The authors surveyed the published clinical trial literatu re on the subject of localized high grade osteosarcoma in order to dev elop new hypotheses dealing with drug-dose combinations in the treatme nt of this disease. METHODS. A computerized literature search was cond ucted to identify all available published reports of the clinical tria ls using high dose methotrexate (MTX) in multidrug protocols treating osteosarcoma. Thirty studies, including discussion of high dose MTX (> 7.5 g/m(2) per course) and precise quantification of 5-year disease f ree survival (DFS), fulfilled the inclusion criteria of this dose-inte nsity analysis. The total number of patients treated in eligible studi es was 1909. Correlation among the planned total doses, the dose inten sities of the drugs, and the 5-year DFS were tested by regression anal ysis. RESULTS. No correlation of any other drug dose or dose intensity with DFS appeared as important as the MTX finding. In multivariate an alysis, the dose intensity of MTX was found to be the one most correla ted with DFS. This correlation appeared to hold for adjuvant and neoad juvant trials. CONCLUSIONS. The dose intensity of MTX seems to be a ma jor factor in predicting the outcome of patients with localized high g rade osteosarcoma. (C) 1996 American Cancer Society.