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Doubts were raised by a multicenter prospective and randomized US study, showing a higher incidence of severe bacterial infections in the rituximab group.Given the high proliferative capacity and aggressiveness of these entities, the CHOP regimen is not sufficient.

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High tumor proliferation determined by Ki-67 or MIB-1 immunohistochemistry has been shown to be an adverse prognostic finding with CHOP chemotherapy, suggesting “kinetic failure” is a problem.

One strategy to overcome kinetic failure is to increase dose density through frequent chemotherapy administration.

The Deutsche Studiengruppe für Hochmaligne Non-Hodgkin Lymphome (DSHNHL) group evaluated the effect of dose density and etoposide in two four-arm studies of CHOP administered every 14 or 21 days, with or without etoposide (CHOEP), in patients older than age 60 years and low-risk patients 60 years and younger.

The CHOP regimen is a first-generation regimen that became the standard after being studied extensively in national cooperative settings.

In the 1980s, single-institution phase II studies of dose-intensive regimens reported impressive response rates compared with historical response rates seen with CHOP therapy.

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