Comparison of BEACOPP and ABVD chemotherapy in intermediate stage Hodgkin's lymphoma: Results of the fourth interim analysis of the HD11 trial of the GHSG

Reviewer: Walter Sall, MD
OncoLink
Last Modified: May 14, 2005

Presenter: B.C. Klimm
Presenter's Affiliation: German Hodgkin's Study Group (GHSG)
Type of Session: Scientific

Background

- Combined modality therapy with 4-6 cycles ABVD and Involved Field Radiation (IFRT) is the standard of care for early, unfavorable prognosis (intermediate stage) Hodgkin's disease (HD).

- Despite high Complete Response (CR) rates, overall treatment failure rates are much higher in this group than in early stage HD.

- Because of favorable outcomes seen in GHSG Hodgkin's trials using BEACOPP chemotherapy in advanced disease, BEACOPP chemotherapy was introduced to intermediate stage patients in this trial (HD 11). An attempt to reduce IFRT dose from 30Gy to 20Gy was also made.

Materials and Methods

- A 2x2 factorial design was employed. Patients received either ABVD x 4 OR BEACOPP x 4 followed by 30Gy IFRT OR 20Gy IFRT.

- Patient eligibility: clinical stage I-IIA with risk factors including bulky mediastinal mass, extranodal disease, elevated ESR or 3 or more sites of disease OR IIB with elevated ESR or 3 or more sites of disease.

- 1422 patients enrolled between 1998 and 2002. 1051 patients evaluable at the time of this interim analysis. Patients well balanced between all treatment arms with regard to age, gender, performance status, pathology and clinical stage. Median follow-up 29.5 months.

Results

- Toxicity: BEACOPP resulted in greater rates of alopecia, leukopenia, infection and anemia while ABVD resulted in greater nausea. Dysphagia was slightly increased with 30Gy IFRT vs. 20Gy.

- Complete Response (CR) rates were 95-97% in all four arms with no significant differences. Death rate was approximately 3% in all arms.

- 34 deaths occurred in total, 13 realted to HD. 9 second malignancies (5 hematologic) were seen.

- Freedom from treatment failure (FFTF) was 90-92% in all arms. 2 year overall survival (OS) was 97.4% for all arms.

Author's Conclusions

- There was no significant difference in rates of CR, FFTF or 2 year OS between any of the 4 arms implying that BEACOPP may be equivalent to ABVD, and 20Gy IFRT may be equivalent to 30Gy in patients receiving chemotherapy.

- The overall FFTF rate of 89.9% at two years is considered unacceptably low by the authors and has led to the introduction of the HD14 trial with increased treatment intensity: 2 cycles escalated BEACOPP with 2 cycles ABVD and 30Gy IFRT vs. 4 cycles ABVD and 30 Gy IFRT

Clinical/Scientific Implications

- BEACOPP holds promise in decreasing the unnacceptably high rates of treatment failure in intermediate stage HD.

- Given the rather high rates of overall failure, this trial cannot be used to support decreasing the IFRT dose from 30Gy to 20Gy.

- Further research in how best to increase dose intensity while still maintaining low toxicity is clearly needed in this group of patients.