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).
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.


METHODS
The trial included patients with normal lactate dehydrogenase (LDH) aged </=60 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-B1 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 </=5% 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 >/=98%, RD <80 </=15%). Addition of etoposide, however, was accompanied by more dose erosion (median RD >/=97%, RD <80 </=17% for CHOEP-21 and </=27% 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 </=60 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.
Wunderlich
A
A
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Kloess
M
M
Reiser
M
M
Rudolph
C
C
Truemper
L
L
Bittner
S
S
Schmalenberg
H
H
Schmits
R
R
Pfreundschuh
M
M
Loeffler
M
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005858:Germany; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D011994:Recombinant Proteins; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D007770:L-Lactate Dehydrogenase; D011241:Prednisone