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Med Pediatr Oncol. 1998 Jul;31(1):1-7.

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status. Study Group of Japan for Treatment of Advanced Neuroblastoma, Tokyo, Japan.

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Department of Pediatric Surgery, University of Tsukuba, Japan.



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 poor-risk group was the purpose of this study.


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 A3, in which cyclophosphamide 1,200 mg/m2 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 A1, which is very similar to regimen A1 that had been used until March 1991 for all patients with advanced neuroblastoma with/without N-myc amplification. The efficacy of regimen A3 was evaluated.


The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A1 and that for the same subgroup of patients treated with regimen A3 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 A1 and those treated with new A1 since March 1991.


Stratification based on N-myc amplification into new A1 and A3 treatment protocols is of significant clinical importance. Regimen A3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

[Indexed for MEDLINE]

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