USE OF COOPERATIVE ONCOLOGY TREATMENT PROTOCOLS ,
AS AN EFFECTIVE WAY TO OBTAIN BETTER SURVIVAL RATES
BRAZILIAN EXPERIENCE WITH PEDIATRIC
ALL (Acute Lymphoblastic Leukemia) STUDIES
November, 2007
BRAZILIAN EXPERIENCE WITH PEDIATRIC ALL (Acute Lymphoblastic Leukemia) STUDIES
FIVE CONSECUTIVE COOPERATIVE ALL PROTOCOLS
• GBTLI ALL-80 ( 203 pts)
• GBTLI ALL-82 ( 335 pts)
• GBTLI ALL-85 ( 456 pts)
• GBTLI ALL-93 ( 867 pts)
• GBTLI ALL-99 (1,142 pts)
Number of registered patients :
Number of institutions: 18 - 83
3,003
BRAZILIAN ALL- 80, - 82 and - 85 PROTOCOLS
TOTAL TREATMENT DURATION
1980
Induction
2,5 years
1982
LR
HR
LR
PVD
+Ciclo
PVD
1985
HR
+Ciclo, Asp
VLR
LR
HR
PVD
PVD
PVD
Ciclo/AraC
↑ HDAraC
WITHOUT CONSOLIDATION / RE-INDUCTION
CNS RT
( Gy )
18 vs 24
24
18
24
without
18
24
CONTINUOUS 6 MP / MTX USE
Maintenance
pulses
Ciclo,
Doxo
No
No
Ciclo, Doxo
VM26,AraC
HR Maintenance
Pulses vs sequential
VCR,DX
VCR, DX
VCR,PRED
VM26, AraC
VCR, DX,VP
VM26, AraC
Induction ( VLR / LR Groups )
4 vs 6 weeks
Objective
18 vs 24Gy (LR)
p Value
NS
NS
NS
N° pts
10 yrs EFS
203
50%
335
55%
456
70%
BRAZILIAN
Induction
ALL-93 PROTOCOL
VLR
LR
Dexa ,VD
Asp , Ara-C
HR
Dexa, VD
↑HD AraC
Consolidation
MTX 2g/m2 IV 24 h inf. X 4
Continuous oral 6MP
Re-induction
PRED, VCR, ASP, 6MP, AraC x 4 wk
RT 12 Gy
Maintenance
therapy
2 years vs 1,6 years Duration
6MP / MTX
Without pulse
Pulse
VCR /DX
N° analyzed pts
853
10 yrs EFS
68 %
Pulses
6MP / MTX
VCR / Pred
↑ AraC, Asp
10 YRS EVENT FREE SURVIVAL IN CHILDREN WITH ALL TREATED BY ALL-93
PROTOCOL ACCORDING TO MAINTENANCE TREATMENT DURATION
1
0,9
0,8
Probability
Probabilidade
0,7
0,6
0,5
0,4
Group 1
0,3
Group 2
0,2
p = 0.377
0,1
0
0
2
4
6
8
10
12
years
EventLivre
FreedeSurvival
Sobrevida
Eventos
Group 1
(1 yr 6 months maintenance therapy) EFS = 74 % ± 2.2 %
( N = 387
In CCR = 289 )
Group 2
(2 yrs maintenance therapy )
( N = 397
In CCR = 304 )
EFS = 73 % ± 2.4 %
BRAZILIAN
Induction
ALL-99 PROTOCOL
LR
HR
Dexa , VD
Asp, AraC
Ciclo , AraC , 6MP
± MTX 1g/m2
IV 6h inf. x 2
Bloc A
Bloc B
Intensification
MTX 2g/m2 IV 4h inf. x 4
Continuous 6MP
DX, VCR , DOXO,
Asp, CICLO, 6TG
Bloc C
Bloc D
Late Consolidation
DX , VCR , DOXO , ASP , Ciclo , 6TG
8 weeks
Maintenance
Therapy
Continuous
6MP / MTX
vs
Intermittent
6MP / MTX
Pulses VCR / DX ( each 8 wk )
N° analyzed pts
6 yrs EFS
1096
68 %
EFS OF LOW-RISK ALL
PTS ( N = 505 ) TREATED BY THE
ALL-99 PROTOCOL , ACCORDING TO MAINTENANCE REGIMEN
1
0,9
0,8
Probability
Probabilidade
0,7
0,6
0,5
0,4
0,3
0,2
p = 0,048
p < 0.01
0,1
0
0
1
2
3
4
5
6
7
8 years
Event Livre
Freede
Survival
Sobrevida
Eventos
Continuous MTX /6MP
Continuous MTX/6MP
Intermittent MTX/6MP
Intermittent MTX / 6MP
EFS = 74.0 % ± 4.6 %
EFS = 88.0 % ± 3.0%
( N = 255
( N = 250
In CCR = 222 )
In CCR = 233 )
6-yr EFS OF HIGH-RISK PTS ( N = 537) ACCORDING TO ALL-99 PROTOCOL
1
0,9
0,8
Probabilidade
Probability
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
0
1
2
3
4
5
6
7
Sobrevida Livre de Eventos
Event Free Survival
6-yrs
EFS
=
59,3 ± 2,7% ( N = 537
In CCR = 351 )
8 years
INCREASING SURVIVAL RATES FOR LOW RISK ALL PEDIATRIC
PATIENTS ( < 18 YEARS ) TREATED WITH THE BRAZILIAN PROTOCOLS
1
0,9
ALL-93
0,8
ALL-99
Probability
0,7
ALL-85
0,6
0,5
ALL-82
0,4
0,3
ALL-80
0,2
0,1
0
0
5
10
15
Event Free Survival
20
25
30 years
INCREASING SURVIVAL RATES FOR HIGH RISK ALL PEDIATRIC
PATIENTS ( < 18 YEARS ) TREATED WITH THE BRAZILIAN PROTOCOLS
1
0,9
0,8
Probability
0,7
ALL-99
0,6
ALL-93
ALL-85
0,5
0,4
ALL-82
0,3
0,2
ALL-80
0,1
0
0
5
10
15
Event Free Survival
20
25
30 years
RECENT RESULTS FROM INTERNATIONAL
PEDIATRIC COOPERATIVE GROUPS
Group
Period
Age
( years )
Pts
N°
Studies
N°
EFS (%)
(8 years)
AIEOP
1982 – 1995
≤ 15
3124
4
65 a 77
BFM
1981 – 1995
≤ 18
4440
4
77 a 83
CCG
1983 – 1995
≤ 21
8832
13
63 a 73
DFCI
1981 – 1995
≤18
1255
4
71 a 77
NOPHO
1981 – 1998
≤ 15
2860
3
54 a 68
POG
1986 - 1994
≤ 21
4408
7
64 a 69
SJCRH
1984 – 1994
≤ 18
711
3
60 a 79
TCCSG
1981 – 1995
≤ 15
1465
4
53 a 65
UKALL
1980 – 1997
≤ 15
4527
3
67 a 81
GBTLI
1980 – 1998
≤ 18
1731
4
50 a 68
Leukemia ( 2000) 14 : 2193-21
LONG
TERM
OVERALL SURVIVAL IN PEDIATRIC
ALL
PTS IN SÃO PAULO CITY
( POPULATION BASED CANCER REGISTRY )
Event Free Survival (months)
CHILDREN FROM
0 – 14 years . PERIOD 1993 AND 1997/ 98
Registro de Câncer de São Paulo, 2004
www.fosp.usp.br/rcsp
SUGGESTED MAIN REASONS FOR THE
UNSUCCESSFUL OUTCOME REGISTERED BY SÃO
PAULO POPULATION BASED CANCER REGISTRY
• Medical Care not performed in only
specialized Pediatric Cancer Centers /
Services
• Lack of hospital beds for acute complications
BRAZILIAN EXPERIENCE WITH PEDIATRIC ALL (Acute Lymphoblastic Leukemia) STUDIES
INSTITUTIONAL AND PROFESSIONAL ACHIEVEMENTS OBTAINED
THROUGH COOPERATIVE TREATMENT PROTOCOLS
• Better diagnosis
• Establishment of Reference Laboratories
• More precise follow-up data
• Establishment of Data Manager Service
• Centrally review data
• New research fields promoted
• National and International cooperation
FUTURE
BRAZILIAN INTERNATIONAL NETWORK COLLABORATION
• Future COG’s Protocol for ALL will randomize conventional
vs
intermittent maintenance therapy for Low Risk patients
• Participation in Epidemiological
ALL Pediatric Studies ( WHO )
• Participation in Environment and Childhood Cancer Studies ( NCI /
WHO / I 4 CCC )
Thank you
for
your attention