Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma

Abstract

consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ ASCR). Total body irradiation (TBI) in the first HDCT/ ASCR and a shorter interval (o12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P ¼ 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year eventfree survival (EFS) (795% confidence interval) for all 52 patients was 62.1713.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P ¼ 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.

Tandem high-dose chemotherapy and autologous stem cell rescue in children with bilateral advanced retinoblastoma

“…[7][8][9][10] This treatment strategy is based on the hypothesis that a dose escalation might improve the survival of children with high-risk solid tumors. Recently, investigators have examined the efficacy of double or tripletandem HDCT/ASCR for further improvements in the outcome of patients with high-risk solid tumors.…”

Ifosfamide, carboplatin, and etoposide for neuroblastoma

“…ICE in lower dosages has activity against various solid tumors, [18][19][20][21][22][23][24][25][26][27][28][29][30][31] but it may be particularly suitable for treating NB. Thus, NB is sensitive to all 3 components, whereas other major pediatric solid tumors (eg, Ewing sarcoma) are relatively resistant to platinum compounds.…”

“…27 The studies pointed to a better response rate of refractory or recurrent sarcomas to this ICE regimen compared with lower dose ICE or 2-drug carboplatin-etoposide or ifosfamide-etoposide regimens. 27 Recently, ICE at dosages higher than in preceding phase 1 studies a) was used as salvage, with major responses in 24/64 (36%) patients treated for primary refractory or progressive NB 28 ; and b) was included in induction regimens for patients with newly diagnosed NB with responses defined according to International Neuroblastoma Response Criteria [29][30][31] (Table 3). In previously untreated patients, ICE achieved a >70% major response rate.…”

“…19,29 Elsewhere, ICE was incorporated into induction after other combinations had been administered. 30,31 Thus, Sung et al initially reserved ICE for NB that was resistant to combined cisplatin, etoposide, doxorubicin, and cyclophosphamide (CEDC) for 5 cycles. 30 Encouraging results (not detailed) prompted a change to alternating cycles of CEDC and ICE in induction.…”

“…30,31 Thus, Sung et al initially reserved ICE for NB that was resistant to combined cisplatin, etoposide, doxorubicin, and cyclophosphamide (CEDC) for 5 cycles. 30 Encouraging results (not detailed) prompted a change to alternating cycles of CEDC and ICE in induction. The report covered 52 patients; induction was followed by tandem transplantation, and the 5-year event-free survival rate was 62.1% AE 13.7%.…”