Six cycles of higher-dose chemotherapy rather than either the standard eight cycles or a lower-dose variant given at shorter time intervals should be the treatment of choice for advanced-stage Hodgkin lymphoma, suggest the findings of a recent study reported in The Lancet. The trial also revealed that positron emission tomography (PET) done after chemotherapy can guide the need for additional radiotherapy.
The research focused on an escalated version of BEACOPP (bleomycin, etoposide, doxorubicin hydrochloride [Adriamycin], cyclophosphamide, vincristine sulfate [Oncovin], procarbazine hydrochloride, and prednisone) chemotherapy, in which the various drugs are administered in higher doses than the doses used in the “baseline” version of BEACOPP14. A team led by Andreas Engert, MD, of the University Hospital of Cologne in Cologne, Germany, randomized more than 2,000 persons aged 18 to 60 years with newly diagnosed advanced-stage Hodgkin lymphoma to receive one of the following three courses of BEACOPP:
- six cycles of BEACOPPescalated (6xBesc group; 711 patients included in the intention-to-treat analysis set)
- the old standard of eight cycles of BEACOPPescalated (8xBesc group; 705 patients included in the intention-to-treat analysis set)
- the lower-dose variant of BEACOPP14 in eight cycles (8xB14 group; 710 patients included in the intention-to-treat analysis set).
Patients with a persistent mass after chemotherapy measuring 2.5 cm or larger and positive on PET scan received additional radiotherapy.
Treatment with six cycles of BEACOPPescalated followed by PET-guided radiotherapy was less toxic and more effective in terms of freedom from treatment failure than were eight cycles of the same chemotherapy regimen. Rates for 5-year freedom from treatment failure were 89.3% for the 6xBesc group, compared with 84.4% for the 8xBesc group and 85.4% for the 8xB14 group. Overall survival rate was significantly better with 6xBesc (95.3%) than with 8xBesc (91.9%); overall survival for 8xB14 was 94.5%.
Mortality was higher in the 8xBesc group (7.5%) than in the 6xBesc (4.6%) and 8xB14 (5.2%) groups, mainly due to differences in treatment-related events (2.1%, 0.8%, and 0.8%, respectively) and secondary malignancies (1.8%, 0.7%, and 1.1%, respectively).
The negative predictive value of PET at 12 months was 94.1%; 225 (11%) of 2,126 patients received additional radiotherapy.