The use of the CHOP regimen (cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), and prednisolone) in the treatment of malignant lymphoma was first described by Gottlieb et al from the MD Anderson Cancer Center in 1973.r The impressive results of the CHOP regimen in lymphoma were subsequently validated in a larger study performed by the Southwest Oncology Group in 1976 (given in 2-weekly and 3-weekly intervals depending on marrow recovery), where it achieved a 4-year disease free survival in the range of 35-45%.r
Over the years, various second generation (M-BACOD, m-BACOD, ProMACE-MOPP) and third generation (ProMACE-CytaBOM, COP-BLAM-III, MACOP-B) regimens have been developed with the aim of improving remission rates and overall survival (OS). A prospective randomised control trial and a meta-analysis of third generation regimens compared with CHOP failed to show any improvement in remission or survival however there was a significant increase in serious toxicity.rr
Further attempts at improving the outcome of CHOP by dose intensification have also been investigated over the years. The German High-grade NHL Study Group (DSHNHL) led by Pfreundschuh et al conducted two clinical trials in patients aged 18-60 (NHL-B1 trial) and in patients aged 61-75 (NHL-B2 trial) with diffuse large B-cell lymphoma (DLBCL). These two trials essentially compared 6 cycles of conventional CHOP delivered every 3 weeks (CHOP-21) with dose intensification in three ways: by adding etoposide (CHOEP-21), reducing the interval between cycles to 2 weeks (CHOP-14), or both (CHOEP-14). The 2-weekly regimens were supported with mandatory prophylactic granulocyte colony-stimulating factor (G-CSF), whereas in the 3-weekly regimens, G-CSF was administered at the treating physician’s discretion.
In the NHL-B1 trial involving patients aged 18-60, CHOEP was associated with the highest CR rate (87.6 vs. 79.4%, P=0.003) and 5-year event-free survival rates (69.2 vs. 57.6%, P=0.004) but not on overall survival. However, both CHOP-14 and CHOEP-14 were found to have equivalent efficacy and were both associated with an improved overall survival when compared with the CHOP-21 and CHOEP-21 schedules (P=0.032).r
In the NHL-B2 trial involving patients aged 61-75, both etoposide-containing arms (CHOEP-14 and CHOEP-21) were associated with significantly more toxicity than the CHOP arms. When the efficacy of CHOP-21 was compared to the other three regimens, only CHOP-14 significantly improved 5-year OS (40.6% with CHOP-21 to 53.3% with CHOP-14).r A more recent study performed by the Japan Clinical Oncology Group had revealed conflicting results. In their Phase III trial comparing 8 cycles of CHOP-14 and CHOP-21 in patients aged 18-69 with DLBCL, there was no detectable difference in PFS and OS.r
The response rate to CHOP has remained consistent over the decades with CR rates ranging from 60 to 76%, with the higher CR rates associated with CHOP-14. Overall survival rates in patients less than 60 years old was noted to be 56% in the most recent 6-year follow-up of the MInT trial,r while in the NHL-B1 trial, 5 year OS rates of 80% was seen in patients with good prognostic features whom received CHOP-14 or -21 (see graph below).
Overall Survival <60 yearsr
© Blood 2010
In patients greater than 60 years old, 5-year OS rates of 40 to 84% have been observed, and 10-year OS rates of 28% have also been recently reported (see graph below).r
© Blood 2010
The most common toxicity associated with CHOP therapy is myelosuppression, with leucopaenia and thrombocytopaenia occurring on days 10 to 14 of the cycle. In the original study by McKelverey et al in 1976,r 18% of patients had neutrophils counts less than 1 x109/L at some stage during therapy, whilst only 5% had platelet counts less than 50 x109/L.
Fisher et al, in their study comparing CHOP with 3rd generation regimens, documented the incidence of grade 5 (fatal) toxicity in the CHOP group at 1% and grade 4 (life-threatening) toxicity at 31% of patients.r
Coiffier et al had compared standard CHOP with Rituximab-CHOP in the 60 to 80 age group, in their pivotal study the following toxicities were documented in the CHOP patients.r
© New England Journal of Medicine 2002