Fast track — ArticlesSix versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60)
Introduction
For more than 25 years, the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen1 has been standard care for aggressive lymphomas.2 The French Groupe de l'Etude des Lymphomes de l'Adulte (GELA) added the monoclonal anti-CD20 antibody rituximab to eight cycles of CHOP (CHOP-21),3 whereas the German High-Grade Non-Hodgkin Lymphoma Study Group (Deutsche Studiengruppe Hochmaligne Lymphome; DSHNHL) shortened intervals between six cycles of treatment with CHOP from 3 weeks to 2 weeks (CHOP-14).4 Both approaches have been shown to improve the outcome of elderly patients, notably without relevant additional toxicity. To compare six cycles with eight cycles of chemotherapy and to address the question whether further improvement could be achieved by adding rituximab to the dose-dense CHOP-14 regimen, the DSHNHL designed the rituximab with CHOP over age 60 years (RICOVER-60) trial, in which elderly patients with diffuse large B-cell lymphoma (DLBCL) were randomly assigned to receive six or eight cycles of chemotherapy, both with and without eight cycles of rituximab. The number of rituximab cycles was kept constant in both R-CHOP-14 arms because we intended to compare the numbers of chemotherapy cycles without the confounder of differing rituximab regimens.
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Patients
Patients were eligible if they had previously untreated, biopsy-confirmed aggressive non-Hodgkin lymphoma of the B-cell type according to the Revised European–American Lymphoma Classification5 (translated into the WHO classification6) and were aged between 61 years and 80 years. Histological diagnosis was reviewed centrally by a panel of five expert haematopathologists. Patients with previous lymphoma associated with acquired immunodeficiency syndrome, diagnosis or history of indolent lymphoma
Results
Between July 1, 2000, and June 14, 2005, 1242 patients were enrolled in 203 institutions in Germany, Czech Republic, and Switzerland. 20 patients were excluded because of missing or retracted informed consent, leaving 1222 for the intention-to-treat analysis (figure 1). There were no significant differences in numbers of excluded patients between treatment regimens. Of the 1222 eligible patients, 307 patients were randomly assigned to receive six cycles of CHOP-14, 305 patients to eight cycles
Discussion
To our knowledge, this trial is the first randomised study to compare six and eight cycles of chemotherapy and assess the role of rituximab in combination with a dose-dense CHOP-14 regimen. Of the three intensified regimens, only six cycles of R-CHOP-14, but not eight cycles of R-CHOP-14, improved event-free survival, progression-free survival, and overall survival over six cycles of CHOP-14. 3-year overall survival of eight cycles of R-CHOP-14 was 5·6% lower than after six cycles of R-CHOP-14.
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