Childhood cancer in Africa French African Pediatric Oncology Group experience Mhamed Harif CHU Mohammed VI, Marrakech, Morocco

Africa Continent Size: 30,065,000 sq km Population: 1,000,000,000 (2009) < 15 years : → 500 M. (2009) More than cancers expected in children each year

Pediatric oncology units in Africa 2000

GFAOP EN Unités pilotes 6 pays africains Algerie : Algiers Oran Cameroon: Yaoundé Madagascar: Antananarivo Maroc: Rabat Casablanca Senegal : Dakar Tunisie : Tunis

North Africa Tunisia1 unit Algeria2 units Morocco2 units West Africa Senegal1 unit Ivory Coast1 unit Mali1 unit Burkina Faso1 unit Togo1 unit Central Africa Cameroon1 unit Congo1 unit Madagascar Antananarivo 1 unit 13 Units French Speaking Africa Pediatric Oncology Units involved 2010

French-African Paediatric Oncology Group GFAOP Created in April  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 US Chest RX Localized stage 4 x vincristine : 1,5 mg/m² 2 x actino : 45  /kg Metastatic stage 6 x vincristine : 1.5 mg/m² 3 x actino : 50 mg/m² Surgery + histology Staging Stage I : 2 courses 4 x vincristine : 1,5 mg/m² 2 x actinomycine D : 45  /kg Stage IV SIOP 2001 schedule good responders Surgery if needed Radiotherapy If necessary and available Stage II and III SIOP 2001

Patients inclusion Nephroblastoma GFAOP STUDIES Study 1 1 st april 2001 to 31 st march 2004 Study 2 1 st april 2005 to 31 st march 2005 Patients registered  excluded at registration 3951 included in the study  excluded after surgery 2973 Patients remaining in the study Nephroblastoma GFAOP STUDIES

Patient Registration by Center Nephroblastoma GFAOP STUDIES

Stage Distribution Based on surgical and/or pathological reports Study 1 Study 2 Nephroblastoma GFAOP STUDIES

Results : All population Nephroblastoma GFAOP STUDIES

Results : Comparison North Africa/ Sub Sahara units Nephroblastoma GFAOP STUDIES

Burkitt Lymphoma 4 studies  Period I: LMB 89 modified protocols Burkitt-GFA 2001 MAT(Morocco –Algeria –Tunisia)  Period II: Cyclo-Burkitt MAT II(Morocco –Algeria – Tunisia) Burkitt lymphoma GFAOP STUDIES

Burkitt-GFAOP 2001 protocol COPCOPM (course 1 and 2)CYM (course 3 and 4) Cyclophosphamide CPM : 300 mg/day IV CPM 500 mg/m²/day IV D1 to 3 Cytarabine 100mg/m²/day SC, D2 to 6 Vincristine 1.5 mg/m² IV, D 1 Vincristine 2 mg/m² IV, D 1 MTX 3 g/m² IV, D1 Prednisone 60 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 – patients enrolled ; included 306  Burkitt-GFAOP 2001 group : 187  MAT group : 119 Patients characteristics  Age : 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 lymphoma GFAOP STUDIES

M.Harif Pediatr Blood Cancer 2008;50:1138–1142 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 lymphoma GFAOP STUDIES

Cyclo-Burkitt : Protocol strategy Diagnostic Cyclophosphamide (1.2 G/M 2 ) MTX IT D1, 8, 15 Complete remission (CR) Stage 1 and 2 Follow up Stage 3 and 4 CPM + IT D28, 43, 57 Follow up No CR Salvage 2 COPM + 2 CYM

N : 254 Burkitt lymphoma GFAOP STUDIES

Cyclo –Burkitt : Staging Burkitt lymphoma GFAOP STUDIES

Burkitt lymphoma GFAOP STUDIES

Burkitt lymphoma GFAOP 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 lymphoma GFAOP STUDIES

MAT LMB 2005 : inclusion 269 pts registered 34 excluded 235 included 209 eligible Burkitt lymphoma GFAOP STUDIES

Patient Registration by Center Nb% Algiers Casablanca Rabat Tunis Total Burkitt lymphoma GFAOP STUDIES

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 : 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 Induction 5 weeks Consolidation 12 weeks Intensification 8 weeks Maintenance 18 months PRD DXM ; VCR ; L Aspa 2 IT PRD ; VCR MTX ; 6 MP 3 IT DXM ; VCR Adria ; 6 MP ; Ara C 2 IT 6 MP ; MTX 9 IT

ALL – GFAOP : first analyzes 4 Units : Cameroon, Madagascar Mali, Senegal 50 patients enrolled 38 confirmed and included 32 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