Intensified Chemotherapy Increases the Survival Rates in Patients With Stage 4 Neuroblastoma With MYCN Amplification

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Abstract

Purpose

Patients with high-risk neuroblastoma who have multiple copies of MYCN fare much worse than do those without MYCN amplification; however, it has not been clarified whether intensified chemotherapy with or without blood stem cell transplantation can alter the extremely poor prognosis of patients with amplified MYCN.

Methods and Results

Between 1985 and 1999, 301 patients older than age 12 months with stage 4 neuroblastoma were treated. From January 1985 to February 1991, 80 patients with stage 4 neuroblastoma with and without MYCN amplification uniformly received induction chemotherapy with regimen A1 (cyclophosphamide 1,200 mg/m2 and vincristine 1.5 mg/m2 on day 1, tetra-hydropyranyl [THP]-Adriamycin 40 mg/m2 on day 3, and cisplatin 90 mg/m2 on day 5). Among 22 patients with MYCN amplification, nine (40.9%) achieved a complete remission and seven (31.8%) underwent stem cell transplantation. Of 58 patients without MYCN amplification, 43 (74.1%) achieved a complete remission and 14 (24.1%) underwent stem cell transplantation. The 5-year relapse-free survival rates were 23.2% for stage 4 patients with MYCN amplification and 33.3% for those without MYCN amplification (P = 0.029); the 5-year overall survival rates were 32.8% for stage 4 patients with MYCN amplification and 42.8% for those without MYCN amplification (P > 0.05). From March 1991 to June 1998, patients with stage 4 neuroblastoma who had 10 or more copies of MYCN were treated with regimen A3 (cyclophosphamide 1,200 mg/m2 per day on days 1 and 2, THP-Adriamycin 40 mg/m2 on day 3, etoposide 100 mg/m2 per day on days 1 to 5, and cisplatin 25 mg/m2 per day on days 1 to 5); those with fewer than 10 copies of MYCN received regimen new A1 (cyclophosphamide 1,200 mg/m2 on day 1, THP-Adriamycin 40 mg/m2 on day 3, etoposide 100 mg/m2 per day on days 1 to 5, and cisplatin 90 mg/m2 on day 5), which is similar in intensity to regimen A1. Among 88 patients with MYCN amplification, 63 (71.6%) achieved a complete remission and 63 (71.68%) underwent stem cell transplantation. Of 133 patients without MYCN amplification, 93 (69.9%) achieved a complete remission and 71 (53.4%) underwent stem cell transplantation. The 5-year relapse-free survival rates were 36.0% for stage 4 patients with MYCN amplification and 32.2% for those without MYCN amplification (P > 0.05), the 5-year overall survival rates were 34.0% for stage 4 patients with MYCN amplification and 38.9% for those without MYCN amplification (P > 0.05). The difference in relapse-free survival rates was significantly different (P = 0.003) between patients with MYCN-amplified tumor treated before (regimen A1) versus after 1991 (regimen A3).

Conclusions

With the use of the more intensive induction regimen A3 plus blood stem cell transplantation for MYCN-amplified patients, survival curves for those with or without MYCN amplification now appear similar. Higher doses of chemotherapy may ameliorate the effect of MYCN amplification in patients with high-risk neuroblastoma.

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