Text Box: ESCALATED DOSE OF CYCLOPHOSPHAMIDE IMPROVED SURVIVAL OF MYCN-AMPLIFIED STAGE 4 NEUROBLASTOMA
Kaneko M1, Tsuchida Y2 (The Study Group of Japan for Neuroblastoma)
1 University of Tsukuba, Tsukuba, Japan
2 Gunma Childrens Medical Center, Gunma, Japan

Objectives: To clarify whether intensified induction chemotherapy can alter the extremely poor prognosis of patients with MYCN amplified stage 4 neuroblastoma aged 1 year or older.
Methods and Results: From January 1985 to February 1991, all patients with stage 4 neuroblastoma uniformly received an induction chemotherapy with regimen A1 (cyclophosphamide 1,200 mg/m2 and vincristine 1.5 mg/m2 on day 1, pirarubicin 40 mg/m2 on day 3, and cisplatin 90 mg/m2 on day 5), regardless of MYCN amplification.  The 5-year relapse-free survival rate was 23.2% for patients with MYCN amplification, and 33.3% for those without MYCN amplification (P=0.029).  From March 1991 to June 1998, stage 4 neuroblastoma patients with amplified MYCN were treated with regimen A3 which consisted of cyclophosphamide 1,200 mg/m2/day on days 1 and 2, pirarubicin 40 mg/m2 on day 3, etoposide 100 mg/m2/day on days 1 to 5, and cisplatin 25 mg/m2/day on days 1 to 5 while stage 4 neuroblastoma patients without MYCN amplification were treated regimen A1. The 5-year relapsed-free survival rate for stage 4 patients with MYCN amplification was 36.0% (63 of 88 patients), and 32.2% for those without MYCN amplification (71 of 133 patients) (P=0.849).
Conclusion: Mainly with the escalated dose of cyclophosphamide in the induction regimen for MYCN-amplified patients, there were no significant difference in survival between patients with MYCN amplified and non- amplified patients. The higher doses in chemotherapy may treat away the ominous effect of MYCN amplification in high-risk neuroblastoma.
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