A kinder and gentler CHOP?

A “kinder and gentler” nation was promised by George Bush in his 1988 acceptance speech to the Republican convention. Within a few years and perhaps with this in mind, Ösby and colleagues (page 3840) of the Nordic Lymphoma Group designed the 2-by-2 study reported in this issue of Blood, attempting to make the CHOP chemotherapy program into a “kinder and gentler” regimen. They identified the “elderly” population (older than 60 years of age) as the target population for this study due to its poorer outcome and tolerance of CHOP chemotherapy.

The CHOP regimen evolved from success with MOPP therapy in Hodgkin disease patients and from the principles of combination chemotherapy. This regimen was designed by J. Gottlieb and DeVita et al (Lancet. 1975;1:248-250) at the NCI in the early 1970s, by incorporating the new anthracycline, doxorubicin, into earlier combination chemotherapy regimens, such as CVP and C-MOPP. Despite numerous attempts over the years to intensify or improve CHOP by adding methotrexate, bleomycin, etoposide, and ara-C, or by scheduling weekly treatments, CHOP has remained the “champ.” Prospectively randomized trials have consistently failed to show an advantage for these second- and third-generation regimens (Fisher et al, N Engl J Med. 1993;328:1002-1006).

Ösby and colleagues pursued another direction in this study. Could CHOP be converted to a more user-friendly regimen for the “elderly” patient who may tolerate it less well? Would the anthracenedione compound, mitoxantrone, substitute for doxorubicin in the CNOP regimen, with less nausea, myelosuppression, and alopecia? Could G-CSF be added to CHOP or CNOP resulting in greater dose intensity and superior outcome? Randomizing 455 patients in 53 centers from 1992 to 1997, the authors now report the answers to these questions to be 2 resounding “no's.” CNOP was clearly less effective than CHOP, nor was time to progression, response, or survival improved by the addition of G-CSF to chemotherapy. An unplanned subset analysis of the CHOP (± G-CSF) groups, however, suggests that G-CSF might improve survival, though this conclusion cannot stand on its own given the design of the study. CHOP remains the undefeated champion, and the ability to improve survival thorough increased dose intensity using growth factors in aggressive lymphoma remains unproven.