A large multicentre trial designed by researchers at the Royal Marsden NHS Foundation Trust BRC and University College London Hospitals BRC , which was managed by the CRUK and UCL Cancer Trials Centre, has provided answers to a hotly debated issue concerning the treatment of aggressive diffuse large B Cell Lymphomas (DLBCL).
Previous studies had raised the possibility that, in these chemosensitive tumours, there may be advantages to giving more intensive therapy and modelling of tumour responses to chemotherapy suggesting that in more indolent lymphomas increased intensity might best be achieved by increasing the doses of the chemotherapy drugs used, whereas in the rapidly growing lymphomas such as DLBCL, intensification might best be achieved by shortening the time-interval between cycles.
In support of this concept in 2004 the German Non-Hodgkin’s Lymphoma study group showed that in DLBCL, CHOP chemotherapy given every 14 days resulted in a superior outcome to CHOP given every 21 days which was the previous standard treatment for DLBC. This time intensification was made possible by the use of recombinant growth factors without a significant increase in toxicity.
These data were obtained, however, before the introduction of the monoclonal anti-CD20 antibody (rituximab) into the therapeutic armamentorium. The addition of rituximab to CHOP chemotherapy has been the biggest advance in the last 40 years, and it was not clear whether, in the post-rituxmab era, there was still an advantage to time-intensification. Therefore, the UK National Cancer Research Institute Lymphoma Clinical Study Group began a large randomised study to compare CHOP-14 (given every 14 days) with CHOP-21 (given every 21 days) in patients receiving rituximab for 6-8 cycles. In this phase 3 trial, over a three-year period 1,080 patients over 18 years old were randomly assigned the two different treatment regimens and the primary outcome measure was overall survival.
Results showed that those who received more frequent cycles of R-CHOP (every two weeks) did not benefit any more than those receiving a cycle every three weeks.
Therefore, R-CHOP given every three weeks remains the standard first-line treatment in patients with this type of non-Hodgkin lymphoma.
