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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-10-3238.
Submitted October 25, 2002
Accepted December 30, 2002
CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial
Eva Osby, Hans Hagberg, Stein Kvaloy, Lasse Teerenhovi, Harald Anderson, Eva Cavallin-Stahl, Harald Holte, John Myhre, Hannu Pertovaara, and Magnus Bjorkholm*
Department of Medicine, Karolinska Hospital, Stockholm, Sweden
Department of Oncology, Uppsala Academic Hospital, Uppsala, Sweden
Department of Oncology, Det Norske Radiumhospital, Oslo, Norway
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
Department of Cancer Epidemiology, Lund University, Lund, Sweden
Department of Oncology, Lund University Hospital, Lund, Sweden
Department of Hematology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark
Department of Oncology, Tampere University Hospital, Tampere, Finland
* Corresponding author; email: magnus.bjorkholm{at}ks.se.
Objective. To test the hypothesis that administration of granulocyte colony-stimulating factor (G-CSF; filgrastim) during CHOP or CNOP induction chemotherapy to elderly patients with aggressive non-Hodgkin's lymphoma (NHL) improves time to treatment failure (TTF), complete remission (CR) rate, and overall survival (OS). Furthermore, the efficacy of CHOP vs CNOP chemotherapy was compared. Methods. 455 previously untreated patients >60 years with stage II-IV aggressive NHL were included in the analysis. Patients (median age 71 years; range 60-86) were randomized to receive CHOP (doxorubicin 50mg/m2) or CNOP (mitoxantrone 10 mg/m2) ± G-CSF (5 [µg/kg from day 2 until day 10-14 of each cycle q 3weeks; 8 cycles). 47 patients previously hospitalized for class I-II congestive heart failure were randomized to receive CNOP ± G-CSF (not included in the CHOP vs CNOP analysis). Results. The CR rates in the CHOP/CNOP + G-CSF and CHOP/CNOP groups were the same, 52%, and in the CHOP ± G-CSF and CNOP ± G-CSF groups 60% and 43% (p<0.001), respectively. No benefit of G-CSF in terms of TTF and OS could be shown (p=0.96, p=0.22, respectively), while CHOP was superior to CNOP (TTF/OS p<0.001). The incidence of severe granulocytopenia (WHO grade III/IV) and granulocytopenic infections were higher in patients not receiving G-CSF. The cumulative proportion of patients receiving  90% of allocated chemotherapy was higher (p<0.05) in patients receiving G-CSF. Conclusion. Concomitant G-CSF treatment did not improve CR rate, TTF or OS. Patients receiving CHOP fared better than those given CNOP chemotherapy. The addition of G-CSF, reduces the incidence of severe granulocytopenia and infections in elderly aggressive NHL patients receiving CHOP or CNOP chemotherapy.
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