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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.
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.