Significantly improved survival outcomes have been demonstrated with the addition of rituximab to first-line CHOP (R-CHOP; cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy administered as a 21-day cycle (CHOP-21) in young and elderly patients with diffuse large B-cell lymphoma (DLBCL). 1 Feugier P Van Hoof A Sebban C et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005; 23: 4117-4126 Crossref PubMed Scopus (1244) Google Scholar , 2 Pfreundschuh M Trumper L Osterborg A et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006; 7: 379-391 Abstract Full Text Full Text PDF PubMed Scopus (1712) Google Scholar , 3 Habermann TM Weller EA Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006; 24: 3121-3127 Crossref PubMed Scopus (1148) Google Scholar Hence, R-CHOP-21 is considered the standard of care for patients with DLBCL. In an effort to improve on the CHOP-21 regimen, Pfreundschuh et al evaluated an intensified CHOP regimen administered every 2 weeks (CHOP-14) and demonstrated an improvement in 5-year event-free survival (EFS) and overall survival (OS) compared with the standard CHOP-21 chemotherapy in patients aged 60 years to 80 years with previously untreated DLBCL. 4 Pfreundschuh M Trumper L Kloess M et al. Twoweekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004; 104: 634-641 Crossref PubMed Scopus (633) Google Scholar Furthermore, the RICOVER-60 trial demonstrated that the addition of rituximab to 6 cycles of CHOP-14 provided a significant survival advantage compared with 6 cycles of CHOP-14 alone in elderly patients with DLBCL. 5 Pfreundschuh M Schubert J Ziepert M et al. Six 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). Lancet Oncol. 2008; 9: 105-116 Abstract Full Text Full Text PDF PubMed Scopus (882) Google Scholar Until recently, results from prospective randomized trials directly comparing R-CHOP-21 and R-CHOP-14 regimens were not available. Cunningham et al conducted a prospective trial to compare the R-CHOP-14 and R-CHOP-21 regimens in newly diagnosed patients with DLBCL. 6 Cunningham D Smith P Mouncey P et al. A phase III trial comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2009; 27 (abstract 8506).: 435s Google Scholar Interim results from this trial demonstrated similar overall response rates (ORRs; 88% vs. 91%; P < .139) and complete responses (CRs)/unconfirmed CRs (CRu; 63% vs. 58%; P < .183) with both regimens. At a median follow-up of 17 months, a 2-year failure-free survival of 74% (95% CI, 71%-77%) and a 2-year OS of 81% (95% CI, 78%-84%) were achieved.