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By F. M. Muggia, J. Henney, V. DeVita Jr. (auth.), Professor Georges Mathé, Professor Franco M. Muggia (eds.)

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Grune and Stratton, New York, pp 215-226 19 Fossati-Bellani F, Gasparini M, Bonadonna G (1979) Adriamycin in the adjuvant treatment of operable osteosarcoma. Recent Results Cancer Res 68: 25-27 20 Glaubiger D, Makuch R, Schwarz J, Levine AS (1979) Influence of prognostic factors on treatment results in Ewing's sarcoma. Proc Am Assoc Clin Oncol 20: 373 24 G. Bonadonna et al. 21 Glucksberg H, Rivkin S, Rasmussen S (1980) Adjuvant chemotherapy in stage II breast cancer. In: Salmon SE, Jones SE (eds) Adjuvant therapy of cancer II.

76 x body weight (kg). Introduction High-dose methotrexate (HDMTX) therapy followed by Leucovorin (citrovorum factor, CF) rescue is based on the assumption that primary resistant tumors have an impaired active membrane transport system for folate compounds which is normally shared by methotrexate (MTX) (Fig. 1). At very high MTX serum concentrations, however, the drug can enter these cells by passive diffusion independent of the active * This work was supported by the Deutsche Forschungsgemeinchaft.

Furthermore, many adjuvant trials use disease-free survival as a major end point for benefit analysis. There are, however, many clinical situations in which disease-free survival might not correlate with increased total survival. , breast cancer and ovarian cancer), and (c) where adjuvant therapy would cause late complications such as chronic organ toxicity and the development of second tumors. Since many patients given adjuvant therapy are potentially cured by their primary surgery and/or radiation, the problem of late complications must be factored into the overall analysis of adjuvant trials.

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