BACOPP-D as treatment in patients with advanced Hodgkin lymphoma

Introduction.
The development of the escalated BEACOPP regimen let to an improved outcome in patients with advanced Hodgkin Lymphoma (HD9 study of the GHSG). However, the application of high dose etoposide (cumulative 4,8 g/m² per 8 cycles) seems to be associated with an
increased incidence of secondary MDS and AML, respectively. Therefore, the aim of our ongoing multicenter pilot study is to evaluate the efficacy
and toxicity of the etoposide free as well as dose intensified BACOPP-D protocol.

Methods.
Since May 2000 a total of 115 patients with Hodgkin Lymphoma (HL) stage IIB, III, and IV were treated with BACOPP-D which included cyclophosphamide 1250 mg/m² (d1), adriamycin 25 mg/m²(d1+2), dacarbazine 250 mg/m² (d1-3), procarbazine 100 mg/m² (d1-7), prednisolone 40 mg/m² (d1-14), bleomycin 10 mg/m²(d8) and vincristine 1,4 mg/m² (maximum 2 mg, d8) at three-weekly intervals with granulocyte colony-stimulating factor (G-CSF). A consolidating involved field radiation (30 Gy) was performed only in patients who achieved less than CR following chemotherapy. Initial staging and post-treatment control included PET monitoring.

Results.
Until now 97 patients (median age 35 years, range 17-65; 61 male, 36 female) are assessable for toxicity and treatment outcome. We analyzed the acute toxicity for 728 cycles of BACOPP-D. CTC/WHO grade III/IV haematological toxicities per patient were observed as follows:
leukopenia 93%, anemia 39%, and thrombocytopenia 33%. CTC grade III/IV non-haematological side effects included documented infection (4%) and lung toxicity (one patient with reversible bleomycininduced pneumonitis). A total of 85 patients (88%) achieved complete remission, 9 patients (9%) achieved partial remission, three patients (3%) had progressive disease. At a median observation time of 39 months (0,9-77 months), six patients have relapsed, and nine deaths were documented (4 HL-specific and 3 treatment related deaths, 1 death due to ruptured Meckel diverticulum with peritonitis, one 65 year-old woman died in CR following myocardial infarction caused by coronary heart disease). One patient developed a second neoplasia (hypopharyngeal carcinoma in an alcoholic). The overall survival and freedom from treatment failure rates at 39 months were 91% and 85%, respectively.

Discussion.
BACOPP-D regimen appears as a feasible and safe treatment protocol with moderate acute toxicity in patients with advanced HL. No secondary AML or MDS occured until now.