Importance of age and methotrexate dosage: prognosis in children and young adults with high-grade osteosarcomas.

The disease-free survival (DFS) in 87 patients with high-grade non-metastatic osteosarcoma of the limbs treated in 3 consecutive pilot studies was compared. From 1978-1982 (Group 1), 41 patients were treated after surgery by adjuvant chemotherapy alternating 2 non-cross resistant cyclic combinations each month for 1 year and early prophylactic lung irradiation. From 1982-1984 (Group 2), preoperative chemotherapy 2-drug combination: adriamycin-cisplatinum (ADR-CDDP) was tested in 20 patients. Surgery was followed by 3 treatment periods of the same combination. From 1984-1987 (Group 3), 26 patients were treated according to modified T-10 protocol with high-dose methotrexate (HDMTX) adapted to age and individual pharmacokinetics. In Group 1, the overall 5 yr DFS was 63% (average follow-up 60.6 months). The worst prognostic factor was low age: 5 yr, DFS under 15 yr was 30%; greater than 15.5 yr, DFS was 85%. The second negative prognostic factor was failure to give sufficient MTX in patients greater than 15 yr. In Group 2, the actuarial 3 yr DFS was only 35% and a low age was still a negative prognostic factor. In Group 3, the 2 yr DFS was 90%, confirming Rosen's results. With HDMTX adapted to age and individual pharmacokinetics, age was no longer a negative prognostic factor. We concluded that HDMTX has a positive effect in the treatment of osteosarcomas in young people; furthermore, in very high doses, as determined by individual pharmacokinetics. In adults, postoperative chemotherapy eventually including moderate doses of MTX, can be effective and may be better tolerated.