From 1982 to 1989, 97 patients with extremity-localized, high-grade
osteosarcoma were treated according to the
T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose
methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (
Cancer 49:1221-1230, 1991). Observed histologic response was no certain
chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative
chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative
cisplatin/
doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial
chemotherapy effect is important for the final outcome in
osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for
tumor response, suggesting a dose-response relationship for HD MTX treatment.