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Front-line topotecan and
high-dose cyclophosphamide followed by ICE in high-risk neuroblastoma
A. Donfrancesco, A. Jenkner, A. Castellano, I. Ilari, G. M. Milano, C.
Dominici, L. De Sio, P. Fidani
Ospedale Bambino Gesł IRCCS, Rome, Italy
Background.
Treatment options for advanced neuroblastoma are still limited, but new agents
have recently shown promising activity.
A pilot study with front-line topotecan was started in April 2001.
Methods.
Two courses of topotecan 6 mg/m2 with cyclophosphamide 4.2 g/m2
(140 mg/kg) were followed by two courses of ICE (ifosfamide 9 g/m2,
carboplatin 800 mg/m2 and etoposide 500 mg/m2), PBSC
harvest, surgery, one course of CAV (cyclophosphamide 3 g/m2,
doxorubicin 75 mg/m2 and vincristine 1.5 mg/m2), high-dose
therapy with ETC (etoposide 600 mg/m2, thiotepa 750 mg/m2
and cyclophosphamide 120 mg/kg) and PBSC rescue (immunoselection),
hyperfractionated local radiotherapy (21 Gy over 7 days) and CRA (160 mg/m2
for 12 months).
10 consecutive pts with high-risk neuroblastoma over one year of age have been
accrued, male/female 6/4, median age 27 mos (range 13-66).
1 stage 2 (MYCNA, 1pdel), 1 stage 3 (MYCNA, 1pdel), 8 stage 4 (2 MYCNA, one 1
pdel).
3 further pts have not yet completed 2 courses.
Results.
Toxicity was predictable and mainly hematological.
Median interval between topo-cyclo courses was 29 days (range 23-34), observed
responses were 1 CR, 4 PR and 5 MR (RR 50%).
Median interval between ICE courses was 31 days (range 23-39), observed
responses at end of induction were 1 CR, 6 PR and 3 MR (RR 70%).
9/10 pts have performed successful PBSC harvests.
After surgery we recorded 5 CR, 4 PR, while 1 pt is TETE.
Median interval between PBSCT and RT was 45 days (range 31-62).
After a median follow-up of 12.5 months (range 4-23), among the 7 pts who have
already completed RT, we recorded 1 DOD (stage 3 MYCNA, 1pdel) 12 months after
diagnosis; 3 CR (stage 4) at +23, +21 and +18 months; 1 VGPR (stage 4) at +9
months; 2 SD (stage 4) at +23 and +13 months.
Conclusions.
Evaluation of the first 10 pts revealed a 100% RR after induction and surgery,
no toxic deaths nor PD during induction, with the potential for adequate PBSC
harvests.
The combination topo-cyclo and ICE was active and well tolerated with promising
results in this high-risk population.
The simple scheme and predictable pattern of toxicity lend themselves to the
incorporation of biological response modifiers and other innovative therapies.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00866,00.asp
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