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Optimization of rituximab for the treatment of DLBCL

Standard

Optimization of rituximab for the treatment of DLBCL : increasing the dose for elderly male patients. / Pfreundschuh, Michael; Murawski, Niels; Zeynalova, Samira; Ziepert, Marita; Loeffler, M; Hänel, Matthias; Dierlamm, Judith; Keller, Ulrich; Dreyling, Martin; Truemper, Lorenz; Frickhofen, Norbert; Hünerlitürkoglu, Ali-Nuri; Schmitz, Norbert; Pöschel, Viola; Rixecker, Tanja; Berdel, Christian; Rübe, Christian; Held, Gerhard; Zwick, Carsten.

in: BRIT J HAEMATOL, Jahrgang 179, Nr. 3, 11.2017, S. 410-420.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Pfreundschuh, M, Murawski, N, Zeynalova, S, Ziepert, M, Loeffler, M, Hänel, M, Dierlamm, J, Keller, U, Dreyling, M, Truemper, L, Frickhofen, N, Hünerlitürkoglu, A-N, Schmitz, N, Pöschel, V, Rixecker, T, Berdel, C, Rübe, C, Held, G & Zwick, C 2017, 'Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients', BRIT J HAEMATOL, Jg. 179, Nr. 3, S. 410-420. https://doi.org/10.1111/bjh.14860

APA

Pfreundschuh, M., Murawski, N., Zeynalova, S., Ziepert, M., Loeffler, M., Hänel, M., Dierlamm, J., Keller, U., Dreyling, M., Truemper, L., Frickhofen, N., Hünerlitürkoglu, A-N., Schmitz, N., Pöschel, V., Rixecker, T., Berdel, C., Rübe, C., Held, G., & Zwick, C. (2017). Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients. BRIT J HAEMATOL, 179(3), 410-420. https://doi.org/10.1111/bjh.14860

Vancouver

Pfreundschuh M, Murawski N, Zeynalova S, Ziepert M, Loeffler M, Hänel M et al. Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients. BRIT J HAEMATOL. 2017 Nov;179(3):410-420. https://doi.org/10.1111/bjh.14860

Bibtex

@article{628ab88abf724de7ad269e4af0c0eff5,
title = "Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients",
abstract = "Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2was not more toxic than 375 mg/m2rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.",
keywords = "Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Dose-Response Relationship, Drug, Doxorubicin, Drug Administration Schedule, Female, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Medication Adherence, Middle Aged, Neoplasm Staging, Prednisone, Prognosis, Rituximab, Sex Factors, Survival Analysis, Treatment Outcome, Vincristine, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
author = "Michael Pfreundschuh and Niels Murawski and Samira Zeynalova and Marita Ziepert and M Loeffler and Matthias H{\"a}nel and Judith Dierlamm and Ulrich Keller and Martin Dreyling and Lorenz Truemper and Norbert Frickhofen and Ali-Nuri H{\"u}nerlit{\"u}rkoglu and Norbert Schmitz and Viola P{\"o}schel and Tanja Rixecker and Christian Berdel and Christian R{\"u}be and Gerhard Held and Carsten Zwick",
note = "{\textcopyright} 2017 John Wiley & Sons Ltd.",
year = "2017",
month = nov,
doi = "10.1111/bjh.14860",
language = "English",
volume = "179",
pages = "410--420",
journal = "BRIT J HAEMATOL",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Optimization of rituximab for the treatment of DLBCL

T2 - increasing the dose for elderly male patients

AU - Pfreundschuh, Michael

AU - Murawski, Niels

AU - Zeynalova, Samira

AU - Ziepert, Marita

AU - Loeffler, M

AU - Hänel, Matthias

AU - Dierlamm, Judith

AU - Keller, Ulrich

AU - Dreyling, Martin

AU - Truemper, Lorenz

AU - Frickhofen, Norbert

AU - Hünerlitürkoglu, Ali-Nuri

AU - Schmitz, Norbert

AU - Pöschel, Viola

AU - Rixecker, Tanja

AU - Berdel, Christian

AU - Rübe, Christian

AU - Held, Gerhard

AU - Zwick, Carsten

N1 - © 2017 John Wiley & Sons Ltd.

PY - 2017/11

Y1 - 2017/11

N2 - Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2was not more toxic than 375 mg/m2rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.

AB - Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2was not more toxic than 375 mg/m2rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Cyclophosphamide

KW - Dose-Response Relationship, Drug

KW - Doxorubicin

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Lymphoma, Large B-Cell, Diffuse

KW - Male

KW - Medication Adherence

KW - Middle Aged

KW - Neoplasm Staging

KW - Prednisone

KW - Prognosis

KW - Rituximab

KW - Sex Factors

KW - Survival Analysis

KW - Treatment Outcome

KW - Vincristine

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/bjh.14860

DO - 10.1111/bjh.14860

M3 - SCORING: Journal article

C2 - 28990173

VL - 179

SP - 410

EP - 420

JO - BRIT J HAEMATOL

JF - BRIT J HAEMATOL

SN - 0007-1048

IS - 3

ER -