Background. It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poorrisk group was the purpose of this study.
Procedure. Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A 3 , in which cyclophosphamide 1,200 mg/m 2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A 1 , which is very similar to regimen A 1 that had been used until March 1991 for all patients with advanced neuroblastoma with/ without N-myc amplification. The efficacy of regimen A 3 was evaluated.
Results. The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A 1 and that for the same subgroup of patients treated with regimen A 3 since March 1991 was 79% and 49%, respectively; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A 1 and those treated with new A 1 since March 1991.
Conclusions. Stratification based on N-myc amplification into new A 1 and A 3 treatment protocols is of significant clinical importance. Regimen A 3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.