Comparison of the two international standards of chemotherapy for patients with early unfavourable or advanced stage Hodgkin lymphoma

Hodgkin lymphoma is a malignancy of the lymphatic system. It is one of the most common cancers in young adults, particularly in their third decade of life, but it occurs also in children and elderly people. Within the last fifty years it has become one of the most curable forms of cancer. To find the best treatment with the greatest efficacy and least toxicity is the most important challenge in treating Hodgkin lymphoma. There are two international standards for the treatment of early unfavourable or advanced stage Hodgkin lymphoma: chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen initiated by the German Hodgkin Study Group (GHSG) and chemotherapy with ABVD (doxorubicin/ bleomycin/ vinblastine/ dacarbazine) regimen, which is widely used because it has been proven to be effective, well tolerated and easy to administer. We aimed to clarify the advantages and disadvantages of both treatments by comparing the chance of survival (overall survival), the chance of recurrence of the tumour and the frequencies of adverse events after treatment in patients with early unfavourable stage or advanced stage Hodgkin lymphoma.

We found five eligible trials but one was unpublished. These trials included only adult patients (16 to 60 years of age). We included 2868 patients in our review. The analysis shows a better chance of avoiding recurrence of the tumour in patients who received chemotherapy including escalated BEACOPP. In those with early unfavourable disease, 22 patients (95% confidence interval (CI) 18 to 29) had to be treated to prevent one tumour recurring within 3.5 years; in patients with advanced disease, 7 patients (95% CI 6 to 10) had to be treated to prevent such an event within 10 years. Treatment with escalated BEACOPP caused a higher risk of adverse events such as anaemia (10 times higher) and thrombocytopenia (19 times higher). However, this did not lead to an increased treatment‐related mortality. In addition, there was an eight times higher risk of secondary acute myeloid leukaemia or myelodysplastic syndromes in patients receiving escalated BEACOPP, but the total number of secondary malignancies did not differ statistically within both treatment groups. Differences regarding overall survival could not be shown, which might be caused by the short follow‐up time (less than five years) of three trials included. Since more than 70% of HL patients survived the first five years due to chemotherapy, the differentiation between regimens might needs more time to become apparent. Thus, a longer follow‐up and the inclusion of the recently closed EORTC 20012 trial will allow a more definitive answer with respect to OS.

Nevertheless, these results can only be extrapolated to adult patients (16 to 60 years of age) with early unfavourable or advanced staged HL. Older patients experience more severe treatment‐related toxicity and a higher mortality during treatment than younger patients, which leads to poorer survival outcome in the elderly. The randomised HD9elderly trial examined BEACOPP baseline compared to COPP/ABVD in patients older than 65 years and showed no statistically significant difference for overall survival (50% overall survival rate at five years in both arms), but an important higher rate of toxic deaths, 21% compared to 8%, after treatment with BEACOPP baseline. Therefore, treatment approaches for elderly patients are different from these for the adults ≤ 60 years and the results of this review are only relevant for adult patients younger than 60 years of age.