Less intense chemotherapy more effective and less toxic for patients with advanced Hodgkin's lymphoma

A study published Online First by The Lancet has found that patients with advanced Hodgkin's lymphoma (a cancer affecting lymph tissue) can be treated more effectively with lower doses of chemotherapy. The study is by Dr Andreas Engert, University Hospital of Cologne, Germany, and colleagues.

In this randomised trial, patients were randomised to receive either eight cycles of a standard regimen with radiotherapy or six cycles plus radiotherapy. BEACOPP14 is given in 2-week intervals in contrast to BEACOPPescalated which is given in 3-week intervals. The dose of various drugs is higher in the BEACOPPescalated regimen as compared to the "baseline" version which is used in BEACOPP14. The authors thus evaluated two different approaches to reduce toxicity of chemotherapy in this new study: one approach used 6 cycles of treatment (6xBEACOPP escalated) instead of 8 (the old standard); the other used the lower dose variant (BEACOPP14) given at shorter time intervals.

Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8× Besc group, 711 in the 6× Besc group, and 710 in the 8×B14 group. Freedom from treatment failure was sequentially non-inferior for the 6× Besc and 8× B14 groups as compared with 8×Besc. 5-year freedom from treatment failure rates were 84% for the 8× Besc group, 89% for 6×Besc group, and 85% for the 8× B14 group. Overall survival in the three groups was 92%, 95%, and 95% respectively, and was significantly better with 6× Besc than with 8×Besc. The 8× Besc group showed a higher mortality (8%) than the 6× Besc (5%) and 8× B14 (5%) groups, mainly due to differences in treatment-related events and secondary cancers.

The authors say: "Treatment with six cycles of BEACOPPescalated followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPPescalated should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting."

They add: "In the HD15 study presented here, we found better overall survival, superior tumour control, and less toxicity with 6 cycles of BEACOPPescalated as compared with eight cycles for treatment of advanced stage Hodgkin's lymphoma. Since the data presented here were generated by a large number of contributing centres from all levels of care, the results of HD15 should help reducing barriers against the use of this effective treatment in advanced stage Hodgkin lymphoma."

In a linked Comment, Dr Olivier Casasnovas, Hôpital le Bocage, Dijon, France, and Dr Bertrand Coiffier, Centre Hospitalier Lyon-Sud, France, say: "Although an important step has been reached towards improvement of the balance of efficacy and toxicity with the upfront BEACOPPescalated regimen in patients with advanced Hodgkin's lymphoma, the future will require additional efforts to identify patients needing fewer than six cycles of BEACOPPescalated."