Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) : a randomised, phase 3, non-inferiority trial
Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Pöschel, Viola - 1971- [verfasserIn] Held, Gerhard Wolfgang - 1968- [verfasserIn] Ziepert, Marita - 1965- [verfasserIn] Witzens-Harig, Mathias [verfasserIn] Holte, Harald [verfasserIn] Thurner, Lorenz - 1982- [verfasserIn] Borchmann, Peter [verfasserIn] Viardot, Andreas - 1968- [verfasserIn] Sökler, Martin - 1965- [verfasserIn] Keller, Ulrich [verfasserIn] Schmidt, Christian [verfasserIn] Truemper, Lorenz [verfasserIn] Mahlberg, Rolf - 1959- [verfasserIn] Marks, Reinhard - 1967- [verfasserIn] Hoeffkes, Heinz-Gert [verfasserIn] Metzner, Bernd [verfasserIn] Dierlamm, Judith [verfasserIn] Frickhofen, Norbert - 1954- [verfasserIn] Hänel, Mathias - 1964- [verfasserIn] Neubauer, Andreas - 1958- [verfasserIn] Kneba, Michael - 1950- [verfasserIn] Merli, Francesco [verfasserIn] Tucci, Alessandra [verfasserIn] de Nully Brown, Peter [verfasserIn] Federico, Massimo [verfasserIn] Lengfelder, Eva - 1951- [verfasserIn] di Rocco, Alice [verfasserIn] Trappe, Ralf Ulrich - 1971- [verfasserIn] Rosenwald, Andreas - 1967- [verfasserIn] Berdel, Christian - 1979- [verfasserIn] Maisenhoelder, Martin [verfasserIn] Shpilberg, Ofer [verfasserIn] Amam, Josif [verfasserIn] Christofyllakis, Konstantinos [verfasserIn] Hartmann, Frank - 1962- [verfasserIn] Murawski, Niels Michael - 1971- [verfasserIn] Stilgenbauer, Stephan - 1966- [verfasserIn] Nickelsen, Maike - 1968- [verfasserIn] Wulf, Gerald [verfasserIn] Glaß, Bertram - 1960- [verfasserIn] Schmitz, Norbert [verfasserIn] Altmann, Bettina [verfasserIn] Löffler, Markus W. - 1978- [verfasserIn] Pfreundschuh, Michael - 1949-2018 [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
19 December 2019 |
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| Anmerkung: |
Gesehen am 30.04.2020 |
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| Umfang: |
11 |
| Übergeordnetes Werk: |
Enthalten in: The lancet - London [u.a.] : Elsevier, 1823, 394(2019), 10216, Seite 2271-2281 |
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| Übergeordnetes Werk: |
volume:394 ; year:2019 ; number:10216 ; pages:2271-2281 ; extent:11 |
| Links: |
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| DOI / URN: |
10.1016/S0140-6736(19)33008-9 |
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| Katalog-ID: |
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| 245 | 1 | 0 | |a Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) |b a randomised, phase 3, non-inferiority trial |c Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh |
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| 520 | |a Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. | ||
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10.1016/S0140-6736(19)33008-9 doi (DE-627)1696975034 (DE-599)KXP1696975034 (OCoLC)1341317775 DE-627 ger DE-627 rda eng Pöschel, Viola 1971- verfasserin (DE-588)1147246068 (DE-627)1008587354 (DE-576)45202188X aut Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh 19 December 2019 11 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 30.04.2020 Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Held, Gerhard Wolfgang 1968- verfasserin (DE-588)121959716 (DE-627)081647948 (DE-576)293018693 aut Ziepert, Marita 1965- verfasserin (DE-588)143050532 (DE-627)641864728 (DE-576)334792827 aut Witzens-Harig, Mathias verfasserin (DE-588)1050736516 (DE-627)784812322 (DE-576)404988970 aut Holte, Harald verfasserin aut Thurner, Lorenz 1982- verfasserin (DE-588)1016795874 (DE-627)705578372 (DE-576)349455260 aut Borchmann, Peter verfasserin (DE-588)107278842X (DE-627)82823762X (DE-576)434245321 aut Viardot, Andreas 1968- verfasserin (DE-588)123546605 (DE-627)082621357 (DE-576)184707498 aut Sökler, Martin 1965- verfasserin (DE-588)1034292501 (DE-627)745191762 (DE-576)381921700 aut Keller, Ulrich verfasserin aut Schmidt, Christian verfasserin aut Truemper, Lorenz verfasserin aut Mahlberg, Rolf 1959- verfasserin (DE-588)112117856 (DE-627)476592305 (DE-576)289721911 aut Marks, Reinhard 1967- verfasserin (DE-588)120105292 (DE-627)080449581 (DE-576)292044402 aut Hoeffkes, Heinz-Gert verfasserin aut Metzner, Bernd verfasserin aut Dierlamm, Judith verfasserin (DE-588)1028107048 (DE-627)730358585 (DE-576)375643672 aut Frickhofen, Norbert 1954- verfasserin (DE-588)1145666302 (DE-627)1006855084 (DE-576)16713535X aut Hänel, Mathias 1964- verfasserin (DE-588)17362295X (DE-627)698532414 (DE-576)134465970 aut Neubauer, Andreas 1958- verfasserin (DE-588)136452981 (DE-627)583296807 (DE-576)301028303 aut Kneba, Michael 1950- verfasserin (DE-588)101170644X (DE-627)659309726 (DE-576)343539187 aut Merli, Francesco verfasserin aut Tucci, Alessandra verfasserin aut de Nully Brown, Peter verfasserin aut Federico, Massimo verfasserin aut Lengfelder, Eva 1951- verfasserin (DE-588)1031229779 (DE-627)736022775 (DE-576)378669230 aut di Rocco, Alice verfasserin aut Trappe, Ralf Ulrich 1971- verfasserin (DE-588)123859344 (DE-627)085485977 (DE-576)293913285 aut Rosenwald, Andreas 1967- verfasserin (DE-588)1111788189 (DE-627)865894868 (DE-576)476255104 aut Berdel, Christian 1979- verfasserin (DE-588)1012547973 (DE-627)704882574 (DE-576)339732474 aut Maisenhoelder, Martin verfasserin aut Shpilberg, Ofer verfasserin aut Amam, Josif verfasserin aut Christofyllakis, Konstantinos verfasserin aut Hartmann, Frank 1962- verfasserin (DE-588)118107186 (DE-627)694674362 (DE-576)302548130 aut Murawski, Niels Michael 1971- verfasserin (DE-588)122720075 (DE-627)706013484 (DE-576)183936256 aut Stilgenbauer, Stephan 1966- verfasserin (DE-588)114728380 (DE-627)590333151 (DE-576)302364781 aut Nickelsen, Maike 1968- verfasserin (DE-588)120390981 (DE-627)696628554 (DE-576)292193645 aut Wulf, Gerald verfasserin aut Glaß, Bertram 1960- verfasserin (DE-588)121205630 (DE-627)705305538 (DE-576)292585462 aut Schmitz, Norbert verfasserin aut Altmann, Bettina verfasserin aut Löffler, Markus W. 1978- verfasserin (DE-588)13832316X (DE-627)696505134 (DE-576)30665346X aut Pfreundschuh, Michael 1949-2018 verfasserin (DE-588)108615871 (DE-627)394701879 (DE-576)289617227 aut Enthalten in The lancet London [u.a.] : Elsevier, 1823 394(2019), 10216, Seite 2271-2281 Online-Ressource (DE-627)270128484 (DE-600)1476593-7 (DE-576)078590159 1474-547X nnns volume:394 year:2019 number:10216 pages:2271-2281 extent:11 https://doi.org/10.1016/S0140-6736(19)33008-9 Verlag Resolving-System lizenzpflichtig Volltext http://www.sciencedirect.com/science/article/pii/S0140673619330089 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 394 2019 10216 2271-2281 11 2013 01 DE-16-250 3646605588 00 --%%-- --%%-- --%%-- --%%-- l01 30-04-20 2013 01 DE-16-250 00 s hd2019 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_44 2013 01 DE-16-250 03 s s_11 2013 01 DE-16-250 04 p (DE-627)147498987X Witzens-Harig, Mathias 2013 01 DE-16-250 04 k (DE-627)1416740783 Medizinische Universitätsklinik und Poliklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_4 2013 01 DE-16-250 05 p (DE-627)1448669367 Lengfelder, Eva 2013 01 DE-16-250 05 k (DE-627)1416468528 III. Medizinische Klinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_26 |
| spelling |
10.1016/S0140-6736(19)33008-9 doi (DE-627)1696975034 (DE-599)KXP1696975034 (OCoLC)1341317775 DE-627 ger DE-627 rda eng Pöschel, Viola 1971- verfasserin (DE-588)1147246068 (DE-627)1008587354 (DE-576)45202188X aut Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh 19 December 2019 11 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 30.04.2020 Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Held, Gerhard Wolfgang 1968- verfasserin (DE-588)121959716 (DE-627)081647948 (DE-576)293018693 aut Ziepert, Marita 1965- verfasserin (DE-588)143050532 (DE-627)641864728 (DE-576)334792827 aut Witzens-Harig, Mathias verfasserin (DE-588)1050736516 (DE-627)784812322 (DE-576)404988970 aut Holte, Harald verfasserin aut Thurner, Lorenz 1982- verfasserin (DE-588)1016795874 (DE-627)705578372 (DE-576)349455260 aut Borchmann, Peter verfasserin (DE-588)107278842X (DE-627)82823762X (DE-576)434245321 aut Viardot, Andreas 1968- verfasserin (DE-588)123546605 (DE-627)082621357 (DE-576)184707498 aut Sökler, Martin 1965- verfasserin (DE-588)1034292501 (DE-627)745191762 (DE-576)381921700 aut Keller, Ulrich verfasserin aut Schmidt, Christian verfasserin aut Truemper, Lorenz verfasserin aut Mahlberg, Rolf 1959- verfasserin (DE-588)112117856 (DE-627)476592305 (DE-576)289721911 aut Marks, Reinhard 1967- verfasserin (DE-588)120105292 (DE-627)080449581 (DE-576)292044402 aut Hoeffkes, Heinz-Gert verfasserin aut Metzner, Bernd verfasserin aut Dierlamm, Judith verfasserin (DE-588)1028107048 (DE-627)730358585 (DE-576)375643672 aut Frickhofen, Norbert 1954- verfasserin (DE-588)1145666302 (DE-627)1006855084 (DE-576)16713535X aut Hänel, Mathias 1964- verfasserin (DE-588)17362295X (DE-627)698532414 (DE-576)134465970 aut Neubauer, Andreas 1958- verfasserin (DE-588)136452981 (DE-627)583296807 (DE-576)301028303 aut Kneba, Michael 1950- verfasserin (DE-588)101170644X (DE-627)659309726 (DE-576)343539187 aut Merli, Francesco verfasserin aut Tucci, Alessandra verfasserin aut de Nully Brown, Peter verfasserin aut Federico, Massimo verfasserin aut Lengfelder, Eva 1951- verfasserin (DE-588)1031229779 (DE-627)736022775 (DE-576)378669230 aut di Rocco, Alice verfasserin aut Trappe, Ralf Ulrich 1971- verfasserin (DE-588)123859344 (DE-627)085485977 (DE-576)293913285 aut Rosenwald, Andreas 1967- verfasserin (DE-588)1111788189 (DE-627)865894868 (DE-576)476255104 aut Berdel, Christian 1979- verfasserin (DE-588)1012547973 (DE-627)704882574 (DE-576)339732474 aut Maisenhoelder, Martin verfasserin aut Shpilberg, Ofer verfasserin aut Amam, Josif verfasserin aut Christofyllakis, Konstantinos verfasserin aut Hartmann, Frank 1962- verfasserin (DE-588)118107186 (DE-627)694674362 (DE-576)302548130 aut Murawski, Niels Michael 1971- verfasserin (DE-588)122720075 (DE-627)706013484 (DE-576)183936256 aut Stilgenbauer, Stephan 1966- verfasserin (DE-588)114728380 (DE-627)590333151 (DE-576)302364781 aut Nickelsen, Maike 1968- verfasserin (DE-588)120390981 (DE-627)696628554 (DE-576)292193645 aut Wulf, Gerald verfasserin aut Glaß, Bertram 1960- verfasserin (DE-588)121205630 (DE-627)705305538 (DE-576)292585462 aut Schmitz, Norbert verfasserin aut Altmann, Bettina verfasserin aut Löffler, Markus W. 1978- verfasserin (DE-588)13832316X (DE-627)696505134 (DE-576)30665346X aut Pfreundschuh, Michael 1949-2018 verfasserin (DE-588)108615871 (DE-627)394701879 (DE-576)289617227 aut Enthalten in The lancet London [u.a.] : Elsevier, 1823 394(2019), 10216, Seite 2271-2281 Online-Ressource (DE-627)270128484 (DE-600)1476593-7 (DE-576)078590159 1474-547X nnns volume:394 year:2019 number:10216 pages:2271-2281 extent:11 https://doi.org/10.1016/S0140-6736(19)33008-9 Verlag Resolving-System lizenzpflichtig Volltext http://www.sciencedirect.com/science/article/pii/S0140673619330089 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 394 2019 10216 2271-2281 11 2013 01 DE-16-250 3646605588 00 --%%-- --%%-- --%%-- --%%-- l01 30-04-20 2013 01 DE-16-250 00 s hd2019 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_44 2013 01 DE-16-250 03 s s_11 2013 01 DE-16-250 04 p (DE-627)147498987X Witzens-Harig, Mathias 2013 01 DE-16-250 04 k (DE-627)1416740783 Medizinische Universitätsklinik und Poliklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_4 2013 01 DE-16-250 05 p (DE-627)1448669367 Lengfelder, Eva 2013 01 DE-16-250 05 k (DE-627)1416468528 III. Medizinische Klinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_26 |
| allfields_unstemmed |
10.1016/S0140-6736(19)33008-9 doi (DE-627)1696975034 (DE-599)KXP1696975034 (OCoLC)1341317775 DE-627 ger DE-627 rda eng Pöschel, Viola 1971- verfasserin (DE-588)1147246068 (DE-627)1008587354 (DE-576)45202188X aut Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh 19 December 2019 11 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 30.04.2020 Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Held, Gerhard Wolfgang 1968- verfasserin (DE-588)121959716 (DE-627)081647948 (DE-576)293018693 aut Ziepert, Marita 1965- verfasserin (DE-588)143050532 (DE-627)641864728 (DE-576)334792827 aut Witzens-Harig, Mathias verfasserin (DE-588)1050736516 (DE-627)784812322 (DE-576)404988970 aut Holte, Harald verfasserin aut Thurner, Lorenz 1982- verfasserin (DE-588)1016795874 (DE-627)705578372 (DE-576)349455260 aut Borchmann, Peter verfasserin (DE-588)107278842X (DE-627)82823762X (DE-576)434245321 aut Viardot, Andreas 1968- verfasserin (DE-588)123546605 (DE-627)082621357 (DE-576)184707498 aut Sökler, Martin 1965- verfasserin (DE-588)1034292501 (DE-627)745191762 (DE-576)381921700 aut Keller, Ulrich verfasserin aut Schmidt, Christian verfasserin aut Truemper, Lorenz verfasserin aut Mahlberg, Rolf 1959- verfasserin (DE-588)112117856 (DE-627)476592305 (DE-576)289721911 aut Marks, Reinhard 1967- verfasserin (DE-588)120105292 (DE-627)080449581 (DE-576)292044402 aut Hoeffkes, Heinz-Gert verfasserin aut Metzner, Bernd verfasserin aut Dierlamm, Judith verfasserin (DE-588)1028107048 (DE-627)730358585 (DE-576)375643672 aut Frickhofen, Norbert 1954- verfasserin (DE-588)1145666302 (DE-627)1006855084 (DE-576)16713535X aut Hänel, Mathias 1964- verfasserin (DE-588)17362295X (DE-627)698532414 (DE-576)134465970 aut Neubauer, Andreas 1958- verfasserin (DE-588)136452981 (DE-627)583296807 (DE-576)301028303 aut Kneba, Michael 1950- verfasserin (DE-588)101170644X (DE-627)659309726 (DE-576)343539187 aut Merli, Francesco verfasserin aut Tucci, Alessandra verfasserin aut de Nully Brown, Peter verfasserin aut Federico, Massimo verfasserin aut Lengfelder, Eva 1951- verfasserin (DE-588)1031229779 (DE-627)736022775 (DE-576)378669230 aut di Rocco, Alice verfasserin aut Trappe, Ralf Ulrich 1971- verfasserin (DE-588)123859344 (DE-627)085485977 (DE-576)293913285 aut Rosenwald, Andreas 1967- verfasserin (DE-588)1111788189 (DE-627)865894868 (DE-576)476255104 aut Berdel, Christian 1979- verfasserin (DE-588)1012547973 (DE-627)704882574 (DE-576)339732474 aut Maisenhoelder, Martin verfasserin aut Shpilberg, Ofer verfasserin aut Amam, Josif verfasserin aut Christofyllakis, Konstantinos verfasserin aut Hartmann, Frank 1962- verfasserin (DE-588)118107186 (DE-627)694674362 (DE-576)302548130 aut Murawski, Niels Michael 1971- verfasserin (DE-588)122720075 (DE-627)706013484 (DE-576)183936256 aut Stilgenbauer, Stephan 1966- verfasserin (DE-588)114728380 (DE-627)590333151 (DE-576)302364781 aut Nickelsen, Maike 1968- verfasserin (DE-588)120390981 (DE-627)696628554 (DE-576)292193645 aut Wulf, Gerald verfasserin aut Glaß, Bertram 1960- verfasserin (DE-588)121205630 (DE-627)705305538 (DE-576)292585462 aut Schmitz, Norbert verfasserin aut Altmann, Bettina verfasserin aut Löffler, Markus W. 1978- verfasserin (DE-588)13832316X (DE-627)696505134 (DE-576)30665346X aut Pfreundschuh, Michael 1949-2018 verfasserin (DE-588)108615871 (DE-627)394701879 (DE-576)289617227 aut Enthalten in The lancet London [u.a.] : Elsevier, 1823 394(2019), 10216, Seite 2271-2281 Online-Ressource (DE-627)270128484 (DE-600)1476593-7 (DE-576)078590159 1474-547X nnns volume:394 year:2019 number:10216 pages:2271-2281 extent:11 https://doi.org/10.1016/S0140-6736(19)33008-9 Verlag Resolving-System lizenzpflichtig Volltext http://www.sciencedirect.com/science/article/pii/S0140673619330089 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 394 2019 10216 2271-2281 11 2013 01 DE-16-250 3646605588 00 --%%-- --%%-- --%%-- --%%-- l01 30-04-20 2013 01 DE-16-250 00 s hd2019 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_44 2013 01 DE-16-250 03 s s_11 2013 01 DE-16-250 04 p (DE-627)147498987X Witzens-Harig, Mathias 2013 01 DE-16-250 04 k (DE-627)1416740783 Medizinische Universitätsklinik und Poliklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_4 2013 01 DE-16-250 05 p (DE-627)1448669367 Lengfelder, Eva 2013 01 DE-16-250 05 k (DE-627)1416468528 III. Medizinische Klinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_26 |
| allfieldsGer |
10.1016/S0140-6736(19)33008-9 doi (DE-627)1696975034 (DE-599)KXP1696975034 (OCoLC)1341317775 DE-627 ger DE-627 rda eng Pöschel, Viola 1971- verfasserin (DE-588)1147246068 (DE-627)1008587354 (DE-576)45202188X aut Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh 19 December 2019 11 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 30.04.2020 Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Held, Gerhard Wolfgang 1968- verfasserin (DE-588)121959716 (DE-627)081647948 (DE-576)293018693 aut Ziepert, Marita 1965- verfasserin (DE-588)143050532 (DE-627)641864728 (DE-576)334792827 aut Witzens-Harig, Mathias verfasserin (DE-588)1050736516 (DE-627)784812322 (DE-576)404988970 aut Holte, Harald verfasserin aut Thurner, Lorenz 1982- verfasserin (DE-588)1016795874 (DE-627)705578372 (DE-576)349455260 aut Borchmann, Peter verfasserin (DE-588)107278842X (DE-627)82823762X (DE-576)434245321 aut Viardot, Andreas 1968- verfasserin (DE-588)123546605 (DE-627)082621357 (DE-576)184707498 aut Sökler, Martin 1965- verfasserin (DE-588)1034292501 (DE-627)745191762 (DE-576)381921700 aut Keller, Ulrich verfasserin aut Schmidt, Christian verfasserin aut Truemper, Lorenz verfasserin aut Mahlberg, Rolf 1959- verfasserin (DE-588)112117856 (DE-627)476592305 (DE-576)289721911 aut Marks, Reinhard 1967- verfasserin (DE-588)120105292 (DE-627)080449581 (DE-576)292044402 aut Hoeffkes, Heinz-Gert verfasserin aut Metzner, Bernd verfasserin aut Dierlamm, Judith verfasserin (DE-588)1028107048 (DE-627)730358585 (DE-576)375643672 aut Frickhofen, Norbert 1954- verfasserin (DE-588)1145666302 (DE-627)1006855084 (DE-576)16713535X aut Hänel, Mathias 1964- verfasserin (DE-588)17362295X (DE-627)698532414 (DE-576)134465970 aut Neubauer, Andreas 1958- verfasserin (DE-588)136452981 (DE-627)583296807 (DE-576)301028303 aut Kneba, Michael 1950- verfasserin (DE-588)101170644X (DE-627)659309726 (DE-576)343539187 aut Merli, Francesco verfasserin aut Tucci, Alessandra verfasserin aut de Nully Brown, Peter verfasserin aut Federico, Massimo verfasserin aut Lengfelder, Eva 1951- verfasserin (DE-588)1031229779 (DE-627)736022775 (DE-576)378669230 aut di Rocco, Alice verfasserin aut Trappe, Ralf Ulrich 1971- verfasserin (DE-588)123859344 (DE-627)085485977 (DE-576)293913285 aut Rosenwald, Andreas 1967- verfasserin (DE-588)1111788189 (DE-627)865894868 (DE-576)476255104 aut Berdel, Christian 1979- verfasserin (DE-588)1012547973 (DE-627)704882574 (DE-576)339732474 aut Maisenhoelder, Martin verfasserin aut Shpilberg, Ofer verfasserin aut Amam, Josif verfasserin aut Christofyllakis, Konstantinos verfasserin aut Hartmann, Frank 1962- verfasserin (DE-588)118107186 (DE-627)694674362 (DE-576)302548130 aut Murawski, Niels Michael 1971- verfasserin (DE-588)122720075 (DE-627)706013484 (DE-576)183936256 aut Stilgenbauer, Stephan 1966- verfasserin (DE-588)114728380 (DE-627)590333151 (DE-576)302364781 aut Nickelsen, Maike 1968- verfasserin (DE-588)120390981 (DE-627)696628554 (DE-576)292193645 aut Wulf, Gerald verfasserin aut Glaß, Bertram 1960- verfasserin (DE-588)121205630 (DE-627)705305538 (DE-576)292585462 aut Schmitz, Norbert verfasserin aut Altmann, Bettina verfasserin aut Löffler, Markus W. 1978- verfasserin (DE-588)13832316X (DE-627)696505134 (DE-576)30665346X aut Pfreundschuh, Michael 1949-2018 verfasserin (DE-588)108615871 (DE-627)394701879 (DE-576)289617227 aut Enthalten in The lancet London [u.a.] : Elsevier, 1823 394(2019), 10216, Seite 2271-2281 Online-Ressource (DE-627)270128484 (DE-600)1476593-7 (DE-576)078590159 1474-547X nnns volume:394 year:2019 number:10216 pages:2271-2281 extent:11 https://doi.org/10.1016/S0140-6736(19)33008-9 Verlag Resolving-System lizenzpflichtig Volltext http://www.sciencedirect.com/science/article/pii/S0140673619330089 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 394 2019 10216 2271-2281 11 2013 01 DE-16-250 3646605588 00 --%%-- --%%-- --%%-- --%%-- l01 30-04-20 2013 01 DE-16-250 00 s hd2019 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_44 2013 01 DE-16-250 03 s s_11 2013 01 DE-16-250 04 p (DE-627)147498987X Witzens-Harig, Mathias 2013 01 DE-16-250 04 k (DE-627)1416740783 Medizinische Universitätsklinik und Poliklinik 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_4 2013 01 DE-16-250 05 p (DE-627)1448669367 Lengfelder, Eva 2013 01 DE-16-250 05 k (DE-627)1416468528 III. Medizinische Klinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_26 |
| allfieldsSound |
10.1016/S0140-6736(19)33008-9 doi (DE-627)1696975034 (DE-599)KXP1696975034 (OCoLC)1341317775 DE-627 ger DE-627 rda eng Pöschel, Viola 1971- verfasserin (DE-588)1147246068 (DE-627)1008587354 (DE-576)45202188X aut Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh 19 December 2019 11 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 30.04.2020 Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Held, Gerhard Wolfgang 1968- verfasserin (DE-588)121959716 (DE-627)081647948 (DE-576)293018693 aut Ziepert, Marita 1965- verfasserin (DE-588)143050532 (DE-627)641864728 (DE-576)334792827 aut Witzens-Harig, Mathias verfasserin (DE-588)1050736516 (DE-627)784812322 (DE-576)404988970 aut Holte, Harald verfasserin aut Thurner, Lorenz 1982- verfasserin (DE-588)1016795874 (DE-627)705578372 (DE-576)349455260 aut Borchmann, Peter verfasserin (DE-588)107278842X (DE-627)82823762X (DE-576)434245321 aut Viardot, Andreas 1968- verfasserin (DE-588)123546605 (DE-627)082621357 (DE-576)184707498 aut Sökler, Martin 1965- verfasserin (DE-588)1034292501 (DE-627)745191762 (DE-576)381921700 aut Keller, Ulrich verfasserin aut Schmidt, Christian verfasserin aut Truemper, Lorenz verfasserin aut Mahlberg, Rolf 1959- verfasserin (DE-588)112117856 (DE-627)476592305 (DE-576)289721911 aut Marks, Reinhard 1967- verfasserin (DE-588)120105292 (DE-627)080449581 (DE-576)292044402 aut Hoeffkes, Heinz-Gert verfasserin aut Metzner, Bernd verfasserin aut Dierlamm, Judith verfasserin (DE-588)1028107048 (DE-627)730358585 (DE-576)375643672 aut Frickhofen, Norbert 1954- verfasserin (DE-588)1145666302 (DE-627)1006855084 (DE-576)16713535X aut Hänel, Mathias 1964- verfasserin (DE-588)17362295X (DE-627)698532414 (DE-576)134465970 aut Neubauer, Andreas 1958- verfasserin (DE-588)136452981 (DE-627)583296807 (DE-576)301028303 aut Kneba, Michael 1950- verfasserin (DE-588)101170644X (DE-627)659309726 (DE-576)343539187 aut Merli, Francesco verfasserin aut Tucci, Alessandra verfasserin aut de Nully Brown, Peter verfasserin aut Federico, Massimo verfasserin aut Lengfelder, Eva 1951- verfasserin (DE-588)1031229779 (DE-627)736022775 (DE-576)378669230 aut di Rocco, Alice verfasserin aut Trappe, Ralf Ulrich 1971- verfasserin (DE-588)123859344 (DE-627)085485977 (DE-576)293913285 aut Rosenwald, Andreas 1967- verfasserin (DE-588)1111788189 (DE-627)865894868 (DE-576)476255104 aut Berdel, Christian 1979- verfasserin (DE-588)1012547973 (DE-627)704882574 (DE-576)339732474 aut Maisenhoelder, Martin verfasserin aut Shpilberg, Ofer verfasserin aut Amam, Josif verfasserin aut Christofyllakis, Konstantinos verfasserin aut Hartmann, Frank 1962- verfasserin (DE-588)118107186 (DE-627)694674362 (DE-576)302548130 aut Murawski, Niels Michael 1971- verfasserin (DE-588)122720075 (DE-627)706013484 (DE-576)183936256 aut Stilgenbauer, Stephan 1966- verfasserin (DE-588)114728380 (DE-627)590333151 (DE-576)302364781 aut Nickelsen, Maike 1968- verfasserin (DE-588)120390981 (DE-627)696628554 (DE-576)292193645 aut Wulf, Gerald verfasserin aut Glaß, Bertram 1960- verfasserin (DE-588)121205630 (DE-627)705305538 (DE-576)292585462 aut Schmitz, Norbert verfasserin aut Altmann, Bettina verfasserin aut Löffler, Markus W. 1978- verfasserin (DE-588)13832316X (DE-627)696505134 (DE-576)30665346X aut Pfreundschuh, Michael 1949-2018 verfasserin (DE-588)108615871 (DE-627)394701879 (DE-576)289617227 aut Enthalten in The lancet London [u.a.] : Elsevier, 1823 394(2019), 10216, Seite 2271-2281 Online-Ressource (DE-627)270128484 (DE-600)1476593-7 (DE-576)078590159 1474-547X nnns volume:394 year:2019 number:10216 pages:2271-2281 extent:11 https://doi.org/10.1016/S0140-6736(19)33008-9 Verlag Resolving-System lizenzpflichtig Volltext http://www.sciencedirect.com/science/article/pii/S0140673619330089 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 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Pöschel, Viola @@aut@@ Held, Gerhard Wolfgang @@aut@@ Ziepert, Marita @@aut@@ Witzens-Harig, Mathias @@aut@@ Holte, Harald @@aut@@ Thurner, Lorenz @@aut@@ Borchmann, Peter @@aut@@ Viardot, Andreas @@aut@@ Sökler, Martin @@aut@@ Keller, Ulrich @@aut@@ Schmidt, Christian @@aut@@ Truemper, Lorenz @@aut@@ Mahlberg, Rolf @@aut@@ Marks, Reinhard @@aut@@ Hoeffkes, Heinz-Gert @@aut@@ Metzner, Bernd @@aut@@ Dierlamm, Judith @@aut@@ Frickhofen, Norbert @@aut@@ Hänel, Mathias @@aut@@ Neubauer, Andreas @@aut@@ Kneba, Michael @@aut@@ Merli, Francesco @@aut@@ Tucci, Alessandra @@aut@@ de Nully Brown, Peter @@aut@@ Federico, Massimo @@aut@@ Lengfelder, Eva @@aut@@ di Rocco, Alice @@aut@@ Trappe, Ralf Ulrich @@aut@@ Rosenwald, Andreas @@aut@@ Berdel, Christian @@aut@@ Maisenhoelder, Martin @@aut@@ Shpilberg, Ofer @@aut@@ Amam, Josif @@aut@@ Christofyllakis, Konstantinos @@aut@@ Hartmann, Frank @@aut@@ Murawski, Niels Michael @@aut@@ Stilgenbauer, Stephan @@aut@@ Nickelsen, Maike @@aut@@ Wulf, Gerald @@aut@@ Glaß, Bertram @@aut@@ Schmitz, Norbert @@aut@@ Altmann, Bettina @@aut@@ Löffler, Markus W. @@aut@@ Pfreundschuh, Michael @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1696975034</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230427121950.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">200430s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/S0140-6736(19)33008-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1696975034</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1696975034</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341317775</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Pöschel, Viola</subfield><subfield code="d">1971-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1147246068</subfield><subfield code="0">(DE-627)1008587354</subfield><subfield code="0">(DE-576)45202188X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)</subfield><subfield code="b">a randomised, phase 3, non-inferiority trial</subfield><subfield code="c">Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">19 December 2019</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">11</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 30.04.2020</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Held, Gerhard Wolfgang</subfield><subfield code="d">1968-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)121959716</subfield><subfield code="0">(DE-627)081647948</subfield><subfield code="0">(DE-576)293018693</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ziepert, Marita</subfield><subfield code="d">1965-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)143050532</subfield><subfield code="0">(DE-627)641864728</subfield><subfield code="0">(DE-576)334792827</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Witzens-Harig, Mathias</subfield><subfield code="e">verfasserin</subfield><subfield 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Pöschel, Viola 1971- 2013 hd2019 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_44 2013 s_11 2013 Witzens-Harig, Mathias 2013 Medizinische Universitätsklinik und Poliklinik 2013 Verfasser 2013 pos_4 2013 Lengfelder, Eva 2013 III. Medizinische Klinik 2013 pos_26 Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial |
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Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh |
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four versus six cycles of chop chemotherapy in combination with six applications of rituximab in patients with aggressive b-cell lymphoma with favourable prognosis (flyer)a randomised, phase 3, non-inferiority trial |
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Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) a randomised, phase 3, non-inferiority trial |
| abstract |
Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Gesehen am 30.04.2020 |
| abstractGer |
Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Gesehen am 30.04.2020 |
| abstract_unstemmed |
Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe. Gesehen am 30.04.2020 |
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Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER) |
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| remote_bool |
true |
| author2 |
Held, Gerhard Wolfgang 1968- Ziepert, Marita 1965- Witzens-Harig, Mathias Holte, Harald Thurner, Lorenz 1982- Borchmann, Peter Viardot, Andreas 1968- Sökler, Martin 1965- Keller, Ulrich Schmidt, Christian Truemper, Lorenz Mahlberg, Rolf 1959- Marks, Reinhard 1967- Hoeffkes, Heinz-Gert Metzner, Bernd Dierlamm, Judith Frickhofen, Norbert 1954- Hänel, Mathias 1964- Neubauer, Andreas 1958- Kneba, Michael 1950- Merli, Francesco Tucci, Alessandra de Nully Brown, Peter Federico, Massimo Lengfelder, Eva 1951- di Rocco, Alice Trappe, Ralf Ulrich 1971- Rosenwald, Andreas 1967- Berdel, Christian 1979- Maisenhoelder, Martin Shpilberg, Ofer Amam, Josif Christofyllakis, Konstantinos Hartmann, Frank 1962- Murawski, Niels Michael 1971- Stilgenbauer, Stephan 1966- Nickelsen, Maike 1968- Wulf, Gerald Glaß, Bertram 1960- Schmitz, Norbert Altmann, Bettina Löffler, Markus W. 1978- Pfreundschuh, Michael 1949-2018 |
| author2Str |
Held, Gerhard Wolfgang 1968- Ziepert, Marita 1965- Witzens-Harig, Mathias Holte, Harald Thurner, Lorenz 1982- Borchmann, Peter Viardot, Andreas 1968- Sökler, Martin 1965- Keller, Ulrich Schmidt, Christian Truemper, Lorenz Mahlberg, Rolf 1959- Marks, Reinhard 1967- Hoeffkes, Heinz-Gert Metzner, Bernd Dierlamm, Judith Frickhofen, Norbert 1954- Hänel, Mathias 1964- Neubauer, Andreas 1958- Kneba, Michael 1950- Merli, Francesco Tucci, Alessandra de Nully Brown, Peter Federico, Massimo Lengfelder, Eva 1951- di Rocco, Alice Trappe, Ralf Ulrich 1971- Rosenwald, Andreas 1967- Berdel, Christian 1979- Maisenhoelder, Martin Shpilberg, Ofer Amam, Josif Christofyllakis, Konstantinos Hartmann, Frank 1962- Murawski, Niels Michael 1971- Stilgenbauer, Stephan 1966- Nickelsen, Maike 1968- Wulf, Gerald Glaß, Bertram 1960- Schmitz, Norbert Altmann, Bettina Löffler, Markus W. 1978- Pfreundschuh, Michael 1949-2018 |
| ppnlink |
270128484 |
| GND_str_mv |
Pöschel, Viola Held, Gerhard Held, Gerhard Wolfgang Jentsch, Marita Ziepert, M. Ziepert, Marita Witzens, Mathias Witzens-Harig, Matthias Harig, Mathias Witzens- Harig, M. Witzens- Witzens-Harig, M. Witzens, M. Witzens-Harig, Mathias Thurner, Lorenz Borchmann, Peter Viardot, Andreas Sökler, M. Sökler, Martin Mahlberg, R. Mahlberg, Rolf Marks, Reinhard Dierlamm, Judith Frickhofen, Norbert Hänel, Mathias Neubauer, Andreas Kneba, Michael Lengfelder, E. Lengfelder, Eva Trappe, Ralf Ulrich Rosenwald, Andreas Berdel, Christian Hartmann, Frank Murawski, Niels Murawski, Niels Michael Stilgenbauer, Stephan Nickelsen, Maike Glaß, Bertram Löffler, Markus Willi Löffler, Markus Löffler, Markus W. Pfreundschuh, Michael |
| GND_txt_mv |
Pöschel, Viola Held, Gerhard Held, Gerhard Wolfgang Jentsch, Marita Ziepert, M. Ziepert, Marita Witzens, Mathias Witzens-Harig, Matthias Harig, Mathias Witzens- Harig, M. Witzens- Witzens-Harig, M. Witzens, M. Witzens-Harig, Mathias Thurner, Lorenz Borchmann, Peter Viardot, Andreas Sökler, M. Sökler, Martin Mahlberg, R. Mahlberg, Rolf Marks, Reinhard Dierlamm, Judith Frickhofen, Norbert Hänel, Mathias Neubauer, Andreas Kneba, Michael Lengfelder, E. Lengfelder, Eva Trappe, Ralf Ulrich Rosenwald, Andreas Berdel, Christian Hartmann, Frank Murawski, Niels Murawski, Niels Michael Stilgenbauer, Stephan Nickelsen, Maike Glaß, Bertram Löffler, Markus Willi Löffler, Markus Löffler, Markus W. Pfreundschuh, Michael |
| GND_txtF_mv |
Pöschel, Viola Held, Gerhard Held, Gerhard Wolfgang Jentsch, Marita Ziepert, M. Ziepert, Marita Witzens, Mathias Witzens-Harig, Matthias Harig, Mathias Witzens- Harig, M. Witzens- Witzens-Harig, M. Witzens, M. Witzens-Harig, Mathias Thurner, Lorenz Borchmann, Peter Viardot, Andreas Sökler, M. Sökler, Martin Mahlberg, R. Mahlberg, Rolf Marks, Reinhard Dierlamm, Judith Frickhofen, Norbert Hänel, Mathias Neubauer, Andreas Kneba, Michael Lengfelder, E. Lengfelder, Eva Trappe, Ralf Ulrich Rosenwald, Andreas Berdel, Christian Hartmann, Frank Murawski, Niels Murawski, Niels Michael Stilgenbauer, Stephan Nickelsen, Maike Glaß, Bertram Löffler, Markus Willi Löffler, Markus Löffler, Markus W. Pfreundschuh, Michael |
| mediatype_str_mv |
c |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| doi_str |
10.1016/S0140-6736(19)33008-9 |
| callnumber-a |
--%%-- |
| up_date |
2024-07-04T14:11:56.245Z |
| _version_ |
1803658006364160000 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1696975034</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230427121950.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">200430s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/S0140-6736(19)33008-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1696975034</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1696975034</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341317775</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Pöschel, Viola</subfield><subfield code="d">1971-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1147246068</subfield><subfield code="0">(DE-627)1008587354</subfield><subfield code="0">(DE-576)45202188X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)</subfield><subfield code="b">a randomised, phase 3, non-inferiority trial</subfield><subfield code="c">Viola Poeschel, Gerhard Held, Marita Ziepert, Mathias Witzens-Harig, Harald Holte, Lorenz Thurner, Peter Borchmann, Andreas Viardot, Martin Soekler, Ulrich Keller, Christian Schmidt, Lorenz Truemper, Rolf Mahlberg, Reinhard Marks, Heinz-Gert Hoeffkes, Bernd Metzner, Judith Dierlamm, Norbert Frickhofen, Mathias Haenel, Andreas Neubauer, Michael Kneba, Francesco Merli, Alessandra Tucci, Peter de Nully Brown, Massimo Federico, Eva Lengfelder, Alice di Rocco, Ralf Trappe, Andreas Rosenwald, Christian Berdel, Martin Maisenhoelder, Ofer Shpilberg, Josif Amam, Konstantinos Christofyllakis, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Maike Nickelsen, Gerald Wulf, Bertram Glass, Norbert Schmitz, Bettina Altmann, Markus Loeffler, Michael Pfreundschuh</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">19 December 2019</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">11</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 30.04.2020</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background - Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. - Methods - This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. - Findings - Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. - Interpretation - In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. - Funding - Deutsche Krebshilfe.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Held, Gerhard Wolfgang</subfield><subfield code="d">1968-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)121959716</subfield><subfield code="0">(DE-627)081647948</subfield><subfield code="0">(DE-576)293018693</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ziepert, Marita</subfield><subfield code="d">1965-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)143050532</subfield><subfield code="0">(DE-627)641864728</subfield><subfield code="0">(DE-576)334792827</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Witzens-Harig, Mathias</subfield><subfield code="e">verfasserin</subfield><subfield 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