Diapositive 1

Traitement de 1re ligne des maladies de Hodgkin tenduesOlivier FitoussiOnco-hmatologuePolyclinique Bordeaux-Nord

22000 2007, 331 patientsTous patients non RC ont un rattrapage et ASCT cond BEAM

PlanQuavons-nous appris depuis 35 ans ?Description de ltudeCritiquesPerspectives et conclusionsEvolution de la chimiothrapieMonothrapieMOPPABVDMOPP/ABVDRgimes intensifsMOPPDL Longo Twenty years of MOPP therapy for Hodgkin's disease JCO, 1986198 patients et suivi de 14 ansRC : 84%OS : 48% 20 ans

MOPPPolychimiothrapie toxiqueHmatotoxicitDigestifSeconds cancersFertilit ++A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin's disease. A cooperative group study by the Cancer and Leukemia Group B. Nissen NI, Pajak TF, Glidewell O, et al. Cancer 1979;43:3140. A dose and time response analysis of the treatment of Hodgkin's disease with MOPP chemotherapy. P Carde, FR MacKintosh and SA Rosenberg Journal of Clinical Oncology, Vol 1, 146-153 Value of prednisone in combination chemotherapy of stage IV Hodgkin's disease. Report from the British National Lymphoma Investigation. Br Med J. 1975 Aug 16;3(5980):413-4.

Evolution de la chimiothrapieMonothrapieMOPPABVDMOPP/ABVDRgimes intensifsCombinaisons versus ABVD seulNCRFFSOSCanellos et al (CALGB)1MOPP x 6 - 8III A/BIV A/BRechute12367%51%66%ABVD x 6 - 811582%61%73%MOPP/ABVD x 1212383%65%75%Somers et al2MOPP x 8IIIAIVA/B9657 %43 %57 %MOPP (2) ABVD (2) x 89659 %60 %65 %Anderson et al (NCI)3MOPP x 6-8III A/BIV A/BRechute69 %48 %66 %ABVD x 6-881 %64 %74 %MOPP /ABVD x 6-882 %64 %76 %1. Canellos GP Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD or MOPP alternating with ABVD. N Engl J Med 19922. Somers R A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alternation of MOPP with ABVD J Clin Oncol 19943.Anderson JR, Canellos GP, MOPP vs. ABVD vs. MOPP alternating with ABVD as treatment for advanced Hodgkin's disease: results at a median follow-up of 4 years. Presented at the Fourth International Conference on Malignant Lymphoma, Lugano, Switzerland, 1990Etude de DUGGAN856 patientsCR: 76% pour ABVD (80% pour MOPP-ABV), P = NSFFS: 63% pour ABVD (66% pour MOPP-ABV), P = NSOS: 82% pour ABVD (81% pour MOPP-ABV), P = NS

Duggan DB, Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. JCO 2003Les conclusions des chimiothrapies alternes/hybridesLABVD semble au moins aussi efficaceLa toxicit semble suprieure dans les rgimes hybrides ou alternsLa survie globale est identiqueConnors JM.Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABVhybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Evolution de la chimiothrapieMonothrapieMOPPABVDMOPP/ABVDRgimes intensifsLong-Term Follow-upAdvanced HL: stages IIB, III, IV

Failure-free survivalOverall survivalYears after study entryCanellos et al. NEJM, 2002

.Duggan D B et al. J Clin Oncol 2003;21:607-614ABVD (8-10 cycles)FFS 5 years: 63%events37%OS 5 years: 82%fatal18%~ 50%Evolution de la chimiothrapieMonothrapieMOPPABVDMOPP/ABVDRgimes intensifs?Efficacy of ABVD (like) in Advanced-Stage HLChemotherapy5-Yr Failure-Free Survival5-Yr Overall SurvivalCanellos 19926-8 ABVD61%73%6 (MOPP+ABVD)65%75%Glick 19986-8 MOPP+ABVD59%77%6-8 MOPP/ABV68%84%Duggan 20038-10 ABVD63%82%8-10 MOPP/ABV66%81%Aleman 20036-8 MOPP/ABV75%83%Ferme 20066-8 ABVPP71% 90%(10y)6-8 MOPP/ABV67%78%GHSG HD94 (COPP+ABVD)68%83%Russo 2009ABVD DD-DI91%GHSG HD94 (COPP+ABVD)68%83%8 BEACOPP esc.88%92%BEACOPP baseline regimenDoseD1D2D3D4D5D6D7D8D9 to D14Started at D9Blemomycin10 mg/m2 (IV)XEtoposide100 mg/m2 (IV)XXXDoxorubicin25 mg/m2 (IV)XCyclophosphamide650 mg/m2 (IV)XVincristine1,4 mg/m2 (IV) [2mg max]XProcarbazine100 mg/m2 (PO)XXXXXXXPrednisone40 mg/m2(PO)XXXXXXXXXG-CSF5 mg/kg/day (SC)XBEACOPPesc regimenDoseD1D2D3D4D5D6D7D8D9 to D14Started at D9Blemomycin10 mg/m2 (IV)XEtoposide200 mg/m2 (IV)XXXDoxorubicin35 mg/m2 (IV)XCyclophosphamide1250 mg/m2 (IV)XVincristine1,4 mg/m2 (IV) [2mg max]XProcarbazine100 mg/m2 (PO)XXXXXXXPrednisone40 mg/m2(PO)XXXXXXXXXG-CSF5 mg/kg/day (SC)XCS IIB-IIIA with risk factorsCS IIIB-IVArm A4 COPP/ABVD RTArm B8 BEACOPP baseline RTArm C8 BEACOPP escalated RTRT to initial bulk and residual tumorGHSG: HD9 Trial Design (1992 - 96)

RandomisationDiehl et al, NEJM, 2003HD9 (GHSG)COPP/ABVDBEACOPPBaselineBEACOPP Escalatedpn263457460CR/CRu85%88%96%5y PFS69%76%87%< 0.055y OS83%88%91%< 0.05Diehl et al, NEJM, 2003Radiotherapy = 69%

HD9 10-years FFTF by treatment armLog-rank tests:A v B v Cp