The Newly Developed Modified BEACOPP-Regimen (BACOPP) Is Active and Feasible in Elderly Patients with Hodgkin Lymphoma: Results of a Phase II Study of the German Hodgkin Study Group (GHSG)

Background: Approximately 20% of patients diagnosed with Hodgkin lymphoma (HL) are more than 60 years of age. These elderly patients still have a poor prognosis, especially when presenting with advanced stages and higher age. The main reason is underdosing of treatment, which is due to reduced tolerability of chemotherapy and age-related comorbidities. In the GHSG experience, elderly patients in the HD9 trial did not profit from the BEACOPP regimen in terms of overall survival, though a better HL specific freedom from treatment failure was achieved as compared to COPP/ABVD. Thus, the GHSG has developed the BACOPP regimen (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which etoposide was omitted to improve tolerability. Further modifications were a 1 week pretreatment phase with vincristine and prednisone, a limitation of vincristine in patients older than 65 years, an increase of the anthracyclines dose, and concomitant application of erythropoietin. Here we report on the final analysis of this multi-center phase II study for elderly patients.

Methods: Between 2004 and 2005, 65 patients with HL in intermediate or advanced stages aged between 60 and 75 years were recruited. Treatment consisted of 6 cycles BACOPP in patients achieving a complete remission (CR) after 4 cycles or 8 cycles BACOPP in case of PR (partial remission) after 4 cycles. The primary endpoints were protocol adherence and response rates. Secondary endpoints included WHO grade III/IV toxicities, Kaplan Meier estimates of progression free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS).

Results: Sixty patients (92%) were eligible for the final analysis. The majority of treatment courses (75%) were administered according to protocol. However, there was a tendency towards reduced dosing in cycles 5 to 8, especially for patients who had reached a CR after 4 cycles of BACOPP. In total, 51 patients showed CR/CRu (85%), 2 PR (3%) and 4 progression of disease (7%). Survival estimates and their 95% confidence intervals are shown in table 1.

Table 1. Kaplan-Meier rates and 95% confidence intervals (CI) for FFTF, PFS and OS.

WHO grade III–IV toxicities were documented in 52 patients (87%). With a median observation time of 33 months, 18 deaths (30%) have been observed. Seven therapy associated fatal outcomes were documented.

Conclusion: The new BACOPP regimen developed for elderly HL patients shows a high CR rate (85%). The FFTF rate at 2 years is within the range known from other schedules in this patient cohort. Overall, the regimen is feasible, but the therapy-associated death rate was high in our patient cohort. Thus, further studies and new approaches are still needed to substantially improve the outcome of elderly patients with early unfavorable or advanced stage HL.