Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group

P. Borchmann, H. Haverkamp, A. Lohri, U. Mey, S. Kreissl, R. Greil, J. Markova, M. Feuring-Buske, J. Meissner, U. Dührsen, H. Ostermann, U. Keller, G. Maschmeyer, G. Kuhnert, M. Dietlein, C. Kobe, H. Eich, C. Baues, H. Stein, M. Fuchs, V. Diehl,...

. 2017 ; 18 (4) : 454-463. [pub] 20170222

Language English Country England, Great Britain

Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial

Persistent link   https://www.medvik.cz/link/bmc17023255
E-resources Online Full text

NLK ProQuest Central from 2000-09-01 to 2 months ago
Nursing & Allied Health Database (ProQuest) from 2000-09-01 to 2 months ago
Health & Medicine (ProQuest) from 2000-09-01 to 2 months ago
Public Health Database (ProQuest) from 2000-09-01 to 2 months ago

Links

PubMed 28236583
DOI 10.1016/s1470-2045(17)30103-1
Knihovny.cz E-resources

BACKGROUND: Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPPescalated) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. METHODS: In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPPescalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPPescalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPPescalated (BEACOPPescalated group) or BEACOPPescalated plus rituximab (R-BEACOPPescalated group). PET-2 was assessed using a 5-point scale with (18)FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPPescalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m(2) (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPPescalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554. FINDINGS: Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPPescalated group (n=220) or the R-BEACOPPescalated group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPPescalated group and 93·0% (89·4-96·6) for those in the R-BEACOPPescalated group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPPescalated group vs 211 [96%] of 220 patients in the R-BEACOPPescalated group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPPescalated group and ten (5%) of 220 in the R-BEACOPPescalated group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPPescalated group and three (1%) in the R-BEACOPPescalated group, all of them due to infection. INTERPRETATION: The addition of rituximab to BEACOPPescalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma. FUNDING: Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17023255
003      
CZ-PrNML
005      
20170720123513.0
007      
ta
008      
170720s2017 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S1470-2045(17)30103-1 $2 doi
035    __
$a (PubMed)28236583
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Borchmann, Peter $u Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany. Electronic address: peter.borchmann@uni-koeln.de.
245    10
$a Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group / $c P. Borchmann, H. Haverkamp, A. Lohri, U. Mey, S. Kreissl, R. Greil, J. Markova, M. Feuring-Buske, J. Meissner, U. Dührsen, H. Ostermann, U. Keller, G. Maschmeyer, G. Kuhnert, M. Dietlein, C. Kobe, H. Eich, C. Baues, H. Stein, M. Fuchs, V. Diehl, A. Engert,
520    9_
$a BACKGROUND: Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPPescalated) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. METHODS: In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPPescalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPPescalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPPescalated (BEACOPPescalated group) or BEACOPPescalated plus rituximab (R-BEACOPPescalated group). PET-2 was assessed using a 5-point scale with (18)FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPPescalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m(2) (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPPescalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554. FINDINGS: Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPPescalated group (n=220) or the R-BEACOPPescalated group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPPescalated group and 93·0% (89·4-96·6) for those in the R-BEACOPPescalated group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPPescalated group vs 211 [96%] of 220 patients in the R-BEACOPPescalated group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPPescalated group and ten (5%) of 220 in the R-BEACOPPescalated group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPPescalated group and three (1%) in the R-BEACOPPescalated group, all of them due to infection. INTERPRETATION: The addition of rituximab to BEACOPPescalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma. FUNDING: Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma.
650    _2
$a dospělí $7 D000328
650    _2
$a protokoly protinádorové kombinované chemoterapie $x terapeutické užití $7 D000971
650    _2
$a bleomycin $x aplikace a dávkování $7 D001761
650    _2
$a cyklofosfamid $x aplikace a dávkování $7 D003520
650    _2
$a doxorubicin $x aplikace a dávkování $7 D004317
650    _2
$a etoposid $x aplikace a dávkování $7 D005047
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a následné studie $7 D005500
650    _2
$a Hodgkinova nemoc $x diagnostické zobrazování $x farmakoterapie $x mortalita $x patologie $7 D006689
650    _2
$a lidé $7 D006801
650    _2
$a mezinárodní agentury $7 D007390
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a lokální recidiva nádoru $x diagnostické zobrazování $x farmakoterapie $x mortalita $x patologie $7 D009364
650    _2
$a staging nádorů $7 D009367
650    _2
$a pozitronová emisní tomografie $x metody $7 D049268
650    _2
$a prednison $x aplikace a dávkování $7 D011241
650    _2
$a prokarbazin $x aplikace a dávkování $7 D011344
650    _2
$a prognóza $7 D011379
650    _2
$a rituximab $x aplikace a dávkování $7 D000069283
650    _2
$a míra přežití $7 D015996
650    _2
$a vinkristin $x aplikace a dávkování $7 D014750
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
700    1_
$a Haverkamp, Heinz $u Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
700    1_
$a Lohri, Andreas $u Cantonal Hospital Baselland, Liestal, Switzerland; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
700    1_
$a Mey, Ulrich $u Cantonal Hospital Graubuenden, Chur, Switzerland; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
700    1_
$a Kreissl, Stefanie $u Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany; German Hodgkin Study Group, Cologne, Germany.
700    1_
$a Greil, Richard $u Third Medical Department, Paracelcus Medical University, Salzburg, Austria.
700    1_
$a Markova, Jana $u University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Feuring-Buske, Michaela $u Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
700    1_
$a Meissner, Julia $u University Hospital of Heidelberg, Heidelberg, Germany.
700    1_
$a Dührsen, Ulrich $u Department of Hematology, University Hospital of Essen, Essen, Germany.
700    1_
$a Ostermann, Helmut $u Department of Internal Medicine III, Klinikum Großhadern, Munich, Germany.
700    1_
$a Keller, Ulrich $u Department of Internal Medicine III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
700    1_
$a Maschmeyer, Georg $u Department of Internal Medicine, Haematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany.
700    1_
$a Kuhnert, Georg $u Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
700    1_
$a Dietlein, Markus $u Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
700    1_
$a Kobe, Carsten $u Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
700    1_
$a Eich, Hans $u Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany.
700    1_
$a Baues, Christian $u Department of Radiotherapy, University Hospital of Cologne, Cologne, Germany.
700    1_
$a Stein, Harald $u Berlin Reference Center for Lymphoma and Haematopathology, Berlin, Germany.
700    1_
$a Fuchs, Michael $u Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany; German Hodgkin Study Group, Cologne, Germany.
700    1_
$a Diehl, Volker $u German Hodgkin Study Group, Cologne, Germany.
700    1_
$a Engert, Andreas $u Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany; German Hodgkin Study Group, Cologne, Germany.
773    0_
$w MED00011558 $t The Lancet. Oncology $x 1474-5488 $g Roč. 18, č. 4 (2017), s. 454-463
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28236583 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20170720 $b ABA008
991    __
$a 20170720124006 $b ABA008
999    __
$a ok $b bmc $g 1238936 $s 984168
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 18 $c 4 $d 454-463 $e 20170222 $i 1474-5488 $m Lancet oncology $n Lancet Oncol. $x MED00011558
LZP    __
$a Pubmed-20170720

Find record

Citation metrics

Archiving options