Childhood cancer in Africa

French African Pediatric

Oncology Group experience

Mhamed HarifCHU Mohammed VI, Marrakech, Morocco

m.harif@menara.ma

Africa

Continent Size:

30,065,000 sq km

Population: 1,000,000,000 (2009)

< 15 years :→ 500 M. (2009)

More than 50 000 cancers expected in children each year

Pediatric oncology units in Africa

2000

GFAOP EN 2000

8 Unités pilotes

6 pays africains

Algerie : Algiers Oran

Cameroon : YaoundéMadagascar : AntananarivoMaroc : Rabat

CasablancaSenegal : DakarTunisie : Tunis

North Africa Tunisia 1 unit Algeria 2 units Morocco 2 units

West Africa Senegal 1 unit Ivory Coast 1 unit Mali 1 unit Burkina Faso 1 unit Togo 1 unit

Central Africa

Cameroon 1 unit Congo 1 unit

Madagascar Antananarivo 1 unit

13 Units

French Speaking Africa

Pediatric Oncology Units involved2010

French-African Paediatric Oncology Group

GFAOP

------- Created in April 2000 -------

Objective : • Improve the management of childhood cancer in Africa• Setting up a database of pediatric cancer in Africa

Methods :• Teaching and training• Improving access to care• Improving awareness regarding pediatric cancer• Developing adapted clinical research programs • Help local support

Teaching and training

Nurses Training in French units (2001 – 2008) : 30 South to South cooperation (Morocco) : 3 French nurses teaching in African Units : 4

Pathology lab. technicians PCD courses (Yaounde) : 3 French lab. (6 months stage) : 2

French-African Paediatric Oncology Group

GFAOP

Physicians

French National Diploma in PO(DIUOP) and 1 year hospital training

• 8 GFAOP members attended and succeeded Short 3 months training in Morocco

• 1 physician Workshops (1 to 3 ) at GFA meetings (1/year).

Teaching and training

French-African Paediatric Oncology Group

GFAOP

Therapeutic research

First study : 2001 – 2004 Objective : Protocol feasibility in “African medical

condition” 2 protocols : Wilms tumor and Burkitt lymphoma

• North Africa : almost unchanged SFCE or SIOP protocol• South to Sahara Units : ‘adapted’, less toxic

Second study : 2005 – 2008 Objectives :

• Improve the first results • Develop new protocols

3 new protocols : • Cyclophosphamide in Burkitt lymphoma• Acute lymphoblastic leukemia • Hodgkin disease

Nephroblastoma

First study : 2001 – 2004

Second study : 2005 – 2008

Nephroblastoma GFAOP STUDIES

GFAOP-Nephro 2001 : Protocol strategy Clinical examination

Abdominal USChest RX

Localized stage

4 x vincristine : 1,5 mg/m²2 x actino : 45 /kg

Metastatic stage

6 x vincristine : 1.5 mg/m²3 x actino : 50 mg/m²

Surgery + histologyStaging

Stage I : 2 courses

4 x vincristine : 1,5 mg/m²2 x actinomycine D : 45 /kg

Stage IV

SIOP 2001 schedule good respondersSurgery if needed

RadiotherapyIf necessary and available

Stage II and III

SIOP 2001

Patients inclusion

Nephroblastoma

GFAOP STUDIES

Study 1

1st april 2001 to 31st march 2004

Study 2

1st april 2005 to

31st march 2005

Patients registered 230 287 excluded at registration 39 51

included in the study 191 236excluded after surgery 29 73

Patients remaining in the study

161 163

Nephroblastoma GFAOP STUDIES

Patient Registration by Center

0

10

20

30

40

50

60

70

80

AbidjanAlger

BamakoCasa

DakarRabat

TanaTunis

Ouaga

Yaoundé

Etude 2001-2004

Etude 2005-2008

Nephroblastoma GFAOP STUDIES

Stage Distribution

24%22%

18% 34%2%

Stade 1 Stade 2 Stade 3

Stade 4 Unknown

8%27%11%

24% 30%

• Based on surgical and/or pathological reports

Study 1

Study 2

Nephroblastoma GFAOP STUDIES

Results :

All population

Nephroblastoma GFAOP STUDIES

GFAOP NEPHROBLASTOMA STUDY N° II OS and EFS ALL PATIENTS

154587177154384177

0,00

0,20

0,40

0,60

0,80

1,00

0 1 2 3

years post surgery

OS N=177

EFS N=177

At risk

85%

82%

GFAOP Nephroblastoma Study 1 O.S. and EFS All population 03/09

123649781041331235467398133

0,00

0,20

0,40

0,60

0,80

1,00

0 1 2 3 4 5

Years post surgery

OS n=133

EFS n=133

71%

69%

Risk

Results :

Comparison North Africa/

Sub Sahara units

Nephroblastoma GFAOP STUDIES

GFAOP NEPHROBLASTOMA STUDY N° I OS and EFS Maghreb and Sub Saharan

748610161832

0,00

0,20

0,40

0,60

0,80

1,00

0 1 2

years post surgery

OS Maghreb N=101

OS Sub Saharan N=32

58%

84%

At risk

GFAOP NEPHROBLASTOMA STUDY N° II OS Maghreb and Sub Saharan

386911771860

0,00

0,20

0,40

0,60

0,80

1,00

0 1 2

years post surgery

OS Maghreb N=117

OS Sub Sahara N=60

At risk

74%

90%

Burkitt Lymphoma

4 studies

Period I: LMB 89 modified protocols 2001-2004

• Burkitt-GFA 2001 • MAT(Morocco –Algeria –Tunisia)

Period II: 2005-2008

• Cyclo-Burkitt• MAT II(Morocco –Algeria – Tunisia)

Burkitt lymphomaGFAOP STUDIES

Burkitt-GFAOP 2001 protocol

COP COPM (course 1 and 2) CYM (course 3 and 4)

CyclophosphamideCPM : 300 mg/day IV

CPM500 mg/m²/day IV D1 to 3

Cytarabine 100mg/m²/day SC, D2 to 6

Vincristine1.5 mg/m² IV, D 1

Vincristine 2 mg/m² IV, D 1

MTX3 g/m² IV, D1

Prednisone60 mg/m² po, D 1 to 5

prednisone 60 mg/m² , D1 to 5

MTX + hydrocortisone: 15mg of each IT, day 2

Methotrexate (MTX)3 g/m² IV, D1

Cyt. 30 mg + Hc 15 mg IT, day 7

MTX + hydrocortisone (Hc)15mg of each IT, D2 and 6 Burkitt lymphoma

GFAOP STUDIES

Burkitt lymphoma : 2001 – 2004

343 patients enrolled ; included

306 Burkitt-GFAOP 2001 group : 187 MAT group : 119

Patients characteristics Age : 1- 17 years (Med : 6y) Sex ratio M/F : 1.9 Tumors main locations

• Abdominal : 242• Facial : 131 Burkitt lymphoma

GFAOP STUDIES

Burkitt lymphoma : 2001 – 2004

Burkitt lymphomaGFAOP STUDIES

M.H

arif

Ped

iatr

Blo

od C

ance

r 20

08;5

0:11

38–1

142

OS according treatment regimen

OS according to year of admission

Burkitt Lymphoma Second studies : 2005 – 2008

North Africa : MAT II protocol

Sub-Sahara units Cyclo-Burkitt GFAOP protocol

Burkitt lymphomaGFAOP STUDIES

Cyclo-Burkitt : Protocol strategy

CYLO BURKITT studyPatients sept 2009

12

93

12

6550

3113

18

12

18 46

24

0

20

40

60

80

100

120M

adagascar

Yaounde

Dakar

Bam

ako

Abid

jan

Ouagadougou

non included

cyclo B study

N : 254

Burkitt lymphomaGFAOP STUDIES

Cyclo –Burkitt : Staging

3%

15%

10%

72% Stage I

Stage II

Stage III

Stage IVBurkitt lymphomaGFAOP STUDIES

GFAOP CYCLO BURKITT2005 - 2009 OS - 254 pts

0,00

0,20

0,40

0,60

0,80

1,00

0 6 12 18 24 30 36months post dg

53%

Burkitt lymphomaGFAOP STUDIES

GFAOP CYCLO BURKITT2005 - 2009 O.S.

0,000,100,200,300,400,500,600,700,800,901,00

0 6 12 18 24 30 36months post dg

st I n= 23 pts st II n= 36 pts

st III n= 187 pts st IV n= 8 pts

81%

46%

GFAOP CYCLO BURKITT2005 - 2009 O.S.

0,000,100,200,300,400,500,600,700,800,901,00

0 6 12 18 24 30 36months post dg

st I n= 23 pts st II n= 36 pts

st III n= 187 pts st IV n= 8 pts

81%

46%

Burkitt lymphomaGFAOP STUDIES

MAT LMB 2005 protocol

Group A : 2 x COPAD

Group B : COP 2 x COPADM 2 x CYM

Group C : COP 2 x COPADM 2 x CYVE Seq 1, 2, 3, 4

Burkitt lymphomaGFAOP STUDIES

MAT LMB 2005 : inclusion

269 pts registered

34 excluded

235 included

209 eligible Burkitt lymphomaGFAOP STUDIES

Patient Registration by Center

Nb %

Algiers 24 10.21

Casablanca 68 28.93

Rabat 121 51.48

Tunis 22 9.36

Total 235 100

Burkitt lymphomaGFAOP STUDIES

GFAOP MAT 2 2005- 2009 study

11254869961382091122446587126209

0,00

0,20

0,40

0,60

0,80

1,00

0 6 12 18 24 30 36months post dg

Overall Survival

Event Free Survival

60%

at risk

Other programs

Hodgkin

ALL

Retinoblastoma

French-African Paediatric Oncology Group

GFAOP

HD-GFAOP protocol strategy

HD – GFAOP : first analyzes

Units participating : 5 Senegal, Madagascar, Mali, Cameroon, Ivory-Cost

Included : 30 Patients characteristics

Age : 2 - 20 years (Med : 9y 9m) Sex ratio M/F : 21/8 Stages :

• I/ II : 8• III : 18• IV : 4

Evaluated : 14 12 CCR 2 relapses

ALL - GFAOP protocol strategy

Induction5 weeks

Consolidation12 weeks

Intensification8 weeks

Maintenance18 months

PRD DXM ; VCR ; L Aspa

2 IT

PRD ; VCRMTX ; 6 MP

3 IT

DXM ; VCR Adria ; 6 MP ; Ara C

2 IT

6 MP ; MTX9 IT

ALL – GFAOP : first analyzes

4 Units : Cameroon, Madagascar Mali, Senegal

50 patients enrolled 38 confirmed and included32 eligible

24 CR (80%) 3 relapses 8 deaths (4 early deaths)

Conclusion

Multicentric and prospecive studies feasible in Africa

Depending on the site : Easier in the North Supportive care is improving XRT missing in the South

Results improving year after year

Challenges

• Tackling abandonment: Information, support for the families, improvement of access to care

• Tackling diagnostic delay

• Improving supportive care

• Ethics

• Data management

• Expanding activity to other cancers,

• Expanding activity to other regions and countries

Groupe Franco-Africain d’Oncology Pediatric