Are treatment related mortality, infertility and second malignancy rates increased with BEACOPP?
Males treated with BEACOPP regimens are at high risk of infertility, with rates of azospermia of approximately 90%.r Low birth rates are observed in women who have been treated for advanced stage Hodgkin lymphoma with a BEACOPP regimen and 34% of females over the age of 30 will undergo menopause.r In the 10 year follow up of HD9 (COPP-ABVD versus SB versus EB) overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, with no significant difference between the arms. If acute myeloid leukaemia alone was considered, the rates were 0.4% (COPP-ABVD), 1.5% (SB), and 3.0% (EB) for the three arms.
A review of 3,412 patients treated with EB on the German HD9, HD12 and HD15r showed an overall treatment related mortality of 1.9%. One third of these deaths occurred in the first cycle. TRM by age group was 0.7% for patients less than 30 years, 2.5% ages 40 to 9, 3.8% ages 50 to 59, and 14.3% for patients age greater than 60 years.
In the most recent Cochrane reviewr, authors concluded that: "The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome (AML/MDS) is increased but efficacy is improved among patients treated with intensified chemotherapy protocols. Treatment decisions must be tailored for individual patients. Consolidating radiotherapy is associated with an increased rate of secondary malignancies; therefore it appears important to define which patients can safely be treated without radiotherapy after chemotherapy, both for early and advanced stages. For early stages, treatment optimisation methods such as use of fewer chemotherapy cycles and reduced field or reduced-dose radiotherapy did not appear to markedly affect efficacy or secondary malignancy risk. Due to the limited amount of long-term follow-up in this meta-analysis, further long-term investigations of late events are needed, particularly with respect to secondary solid tumours. Since many older studies have been included, possible improvement of radiotherapy techniques must be considered when interpreting these results".
Six cycles of EB in advanced stage Hodgkin lymphoma, defined as IIB with a large mediastinal mass greater than 1/3 chest diameter or with extranodal lesions, all stages III-IVr in patients up to the age of 60 probably provides a 7 to 10% survival advantage over ABVD, but is associated with a higher incidence of infertility, as well as being a more toxic and complex regimen to deliver. There is no established role for SB or BEACOPP14, which have been shown to be inferior to six cycles of EB. The protocol should not be used in patients older than 60.