Practicability and acute haematological toxicity of 2-and 3-weekly CHOP and CHOEP chemotherapy for aggressive non-Hodgkin's lymphoma: results from the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)

被引:81
作者
Wunderlich, A
Kloess, M
Reiser, M
Rudolph, C
Truemper, L
Bittner, S
Schmalenberg, H
Schmits, R
Pfreundschuh, M
Loeffler, M
机构
[1] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04103 Leipzig, Germany
[2] Univ Cologne, Clin Internal Med 1, Cologne, Germany
[3] Carl Thiem Hosp, Clin Haematol & Internal Oncol, Cottbus, Germany
[4] Univ Gottingen, Clin Internal Med, D-3400 Gottingen, Germany
[5] Univ Hosp Hamburg Eppendorf, Dept Haematol & Oncol, Hamburg, Germany
[6] Univ Jena, Dept Internal Med 2, D-6900 Jena, Germany
[7] Univ Saarland, Clin Internal Med 1, D-6650 Homburg, Germany
关键词
aggressive lymphomas; CHOP regimen; clinical study; relative dose toxicity;
D O I
10.1093/annonc/mdg249
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: There is evidence that intensified variants of the classical 3-weekly CHOP-21 chemotherapy [cyclophosphamide (C), doxorubicin (H), vincristine (O), prednisone (P)] may improve treatment outcome in aggressive lymphoma. Three variants using either an addition of etoposide (CHOEP-21: 100 mg/m(2) on days 1-3), the shortening to 2-week intervals using recombinant human granulocyte colony-stimulating factor (rhG-CSF; CHOP-14) or both (CHOEP-14) are currently compared with CHOP-21 in the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). To enable more extensive testing of these schemes we here characterise their practicability regarding schedule adherence, acute haematotoxicity and need for supportive treatment. Patients and methods: The trial included patients with normal lactate dehydrogenase (LDH) aged less than or equal to60 years (NHL-B1) and patients aged 61-75 years (NHL-B2). The data are taken from an interim analysis. Data from 959 patients (CHOP-21: 232; CHOP-14: 238; CHOEP-21: 244; CHOEP-14: 245) from 162 institutions with a total of 5331 therapy cycles were evaluated. Results: The dose adherence in the NHL-B 1 trial was excellent. The median relative dose (RD; i.e. actually given compared to planned dose) exceeds 98% for the myelosuppressive drugs in all four regimens. Only less than or equal to5% of patients received a relative dose <80% (RD <80). The median treatment duration could be shortened as scheduled for both CHOP-14 by 36 days and CHOEP-14 by 35 days. The dose adherence in the NHL-B2 trial was excellent for CHOP-21 and CHOP-14 for the myelosuppressive drugs (median RD greater than or equal to98%, RD <80 <= 15%). Addition of etoposide, however, was accompanied by more dose erosion (median RD >= 97%, RD <80 less than or equal to17% for CHOEP-21 and less than or equal to27% for CHOEP-14). The median treatment duration could be shortened by 34 days with CHOP-14 compared with CHOP-21. Less treatment shortening was feasible for CHOEP-14 compared with CHOP-21 (median of 29 days). CHOP-14 and CHOP-21 were similar regarding toxicity profile, rate of infection, use of antibiotics, rate of transfusions and hospitalisation. CHOEP schemes were associated with a higher rate of infections, more transfusion requirements, more antibiotic use and longer hospitalisation than the CHOP schemes, particularly in patients aged >60 years. Haematopoietic recovery was age- and treatment-related. Conclusions: CHOP-14 with the addition of rhG-CSF is safe and practicable in a large multicentre setting in patients aged 18-75 years. Despite shorter treatment intervals it can be delivered at the same dose as the classical 3-weekly CHOP with a comparable toxicity profile. The addition of etoposide is feasible and safe for patients less than or equal to60 years old in both the CHOEP-21 and CHOEP-14 schemes. For patients >60 years of age the addition of etoposide is associated with marked dose erosion due to increased toxicity. In this age group CHOEP should be used with caution.
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页码:881 / 893
页数:13
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