Optimization of Rituximab for the Treatment of Diffuse Large B-Cell Lymphoma (II): Extended Rituximab Exposure Time in the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group

被引：65

作者：

Pfreundschuh, Michael ^{[1
]}

Poeschel, Viola ^{[1
]}

Zeynalova, Samira ^{[2
]}

Haenel, Mathias ^{[3
]}

Held, Gerhard ^{[1
]}

Schmitz, Norbert ^{[4
]}

Viardot, Andreas ^{[5
]}

Dreyling, Martin H. ^{[6
]}

Hallek, Michael ^{[8
]}

Mueller, Carsten ^{[8
]}

Wiesen, Martin H. J. ^{[8
]}

Witzens-Harig, Mathias ^{[9
]}

Truemper, Lorenz ^{[10
]}

Keller, Ulrich ^{[7
]}

Rixecker, Tanja ^{[1
]}

Zwick, Carsten ^{[1
]}

Murawski, Niels ^{[1
]}

机构：

[1] Univ Klinikum Saarlandes, Homburg, Germany

[2] Univ Leipzig, D-04109 Leipzig, Germany

[3] Klinikum Chemnitz, Chemnitz, Germany

[4] Asklepios Klin St Georg, Hamburg, Germany

[5] Univ Ulm Klinikum, Ulm, Germany

[6] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany

[7] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany

[8] Univ Cologne, D-50931 Cologne, Germany

[9] Univ Klin Heidelberg, Heidelberg, Germany

[10] Univ Klinikum Gottingen, Gottingen, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2014年 / 32卷 / 36期

关键词：

CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; DOSE-DENSE RITUXIMAB; ELDERLY-PATIENTS; CHOP CHEMOTHERAPY;

D O I：

10.1200/JCO.2013.54.6861

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6xR-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6xR-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. Results The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. Conclusion Extended rituximab exposure compared with eight 2-week applications in combination with 6xR-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6xR-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted. (C) 2014 by American Society of Clinical Oncology

引用

页码：4127 / U354

页数：8

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