- 作者：Andreas Engert ; MDa ; b ; a.engert@uni-koeln.de ; Heinz Haverkamp ; PhDb ; * ; Carsten Kobe ; MDc ; * ; Jana Markova ; MDd ; Christoph Renner ; MDe ; Antony Ho ; MDf ; José ; e Zijlstra ; MDg ; Zdenek Krá ; l ; MDh ; Michael Fuchs ; MDb ; Michael Hallek ; MDa ; Lothar Kanz ; MDi ; Hartmut Dö ; hner ; MDj ; Bernd Dö ; rken ; MDk ; Nicole Engel ; MDl ; Max Topp ; MDm ; Susanne Klutmann ; MDn ; Holger Amthauer ; MDo ; Andreas Bockisch ; MDp ; Regine Kluge ; MDq ; Clemens Kratochwil ; MDr ; Otmar Schober ; MDs ; Richard Greil ; MDt ; Reinhard Andreesen ; MDu ; Michael Kneba ; MDv ; Michael Pfreundschuh ; MDw ; Harald Stein ; MDx ; Hans Theodor Eich ; MDy ; Rolf-Peter Mü ; ller ; MDy ; Markus Dietlein ; MDc ; Peter Borchmann ; MDb ; Volker Diehl ; MDb ; on behalf of the German Hodgkin Study Group ; the Swiss Group for Clinical Cancer Research ; the Arbeitsgemeinschaft Medikamentö ; se Tumortherapie&dagger ;
- 刊名：The Lancet
- 出版年：2012
- 出版时间：12-18 May, 2012
- 年：2012
- 卷：379
- 期：9828
- 页码：1791-1799
- 全文大小：326 K
ass=""h3"">Summary
ass=""h4"">Background
The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy.ass=""h4"">Methods
In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPPescalated (8¡ÁBesc group), six cycles of BEACOPPescalated (6¡ÁBesc group), or eight cycles of BEACOPP14 (8¡ÁB14 group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2¡¤5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041.
ass=""h4"">Findings
Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8¡ÁBesc group, 711 in the 6¡ÁBesc group, and 710 in the 8¡ÁB14 group. Freedom from treatment failure was sequentially non-inferior for the 6¡ÁBesc and 8¡ÁB14 groups as compared with 8¡ÁBesc. 5-year freedom from treatment failure rates were 84¡¤4 % (97¡¤5 % CI 81¡¤0-87¡¤7) for the 8¡ÁBesc group, 89¡¤3 % (86¡¤5-92¡¤1) for 6¡ÁBesc group, and 85¡¤4 % (82¡¤1-88¡¤7) for the 8¡ÁB14 group (97¡¤5 % CI for difference between 6¡ÁBesc and 8¡ÁBesc was 0¡¤5-9¡¤3). Overall survival in the three groups was 91¡¤9 % , 95¡¤3 % , and 94¡¤5 % respectively, and was significantly better with 6¡ÁBesc than with 8¡ÁBesc (97¡¤5 % CI 0¡¤2-6¡¤5). The 8¡ÁBesc group showed a higher mortality (7¡¤5 % ) than the 6¡ÁBesc (4¡¤6 % ) and 8¡ÁB14 (5¡¤2 % ) groups, mainly due to differences in treatment-related events (2¡¤1 % , 0¡¤8 % , and 0¡¤8 % , respectively) and secondary malignancies (1¡¤8 % , 0¡¤7 % , and 1¡¤1 % , respectively). The negative predictive value for PET at 12 months was 94¡¤1 % (95 % CI 92¡¤1-96¡¤1); and 225 (11 % ) of 2126 patients received additional radiotherapy.
ass=""h4"">Interpretation
Treatment with six cycles of BEACOPPescalated followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPPescalated should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting.
ass=""h4"">Funding
Deutsche Krebshilfe and the Swiss Federal Government.