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Recurrent neuroblastoma:
Randomized treatment with topotecan + cyclophosphamide (T+C) vs. topotecan
alone(T). A POG/CCG Intergroup Study
C. N. Frantz, W. B. London, L. Diller, R. Seeger, K. Sawyer
Dupont Hospital, Wilmington, DE; COG Statistics Dept,
Gainesville, FL; Dana-Farber Cancer Institute, Boston, MA; Childrens Hospital
Los Angeles, Los Angeles, CA; University of Maryland, Baltimore, MD.
Background.
In Phase I/II studies, T and the combination of T+C each
demonstrated promising activity against recurrent neuroblastoma, so a randomized
study was performed.
Methods.
Eligible patients were <21 yrs with evaluable disease at
first recurrence after a first regimen of aggressive chemotherapy.
73 patients had prior stem cell transplants.
13 patients received “therapeutic window” deferoxamine for 3-6 weeks as part
of the study.
T+C received T 0.75mg/m2+C 250mg/m2+MESNA 150 mg/m2 dailyX5d q21d.
T received T 2.4mg/m2/dX5d q21d.
Best response according to the International Neuroblastoma Response Criteria was
analyzed in a two-stage sequential design.
In the calculation of time to progressive disease, patients taken off study for
stem cell transplant, refusal, or unrelated death were censored at that
time.
Results.
Target accrual 118, accrual 123, eligible 119 patients
(1996-2001).
Hematopoietic toxicity was the same in both arms.
Deferoxamine had no effect on outcome.
There were 11 (19%) CR+PR on T, 18 (31%) on T+C; 19 (32%) CR+PR+MR on T, 26
(45%) on T+C.
At least eight more responders in T+C than in T were required by the two-stage
design in order to conclude superiority of T+C; with only seven, there is
insufficient evidence to reach such a conclusion.
For both EFS and S treatment comparisons, the curves were not significantly
different.
However, the time to disease progression was significantly longer for T+C.
The 2-year Progression-Free Survival rates (+/- standard error) were 16%+/-6%
(T) vs. 36%+/-9% (T+C), p=0.0379.
Conclusions.
There is a trend toward better results with T+C than
T.
Incorporation of the combination into front line treatment plans deserves
further exploration.
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_19-00765,00.asp
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