Reduction of Combined Modality Treatment Intensity in Early Stage Hodgkin’s Lymphoma: Interim Analysis of the HD 10 Trial of the GHSG.

Background: Combined modality treatment of chemotherapy (usually ABVD) followed by involved field irradiation (IF) is today a standard treatment regimen for early stage Hodgkin′s lymphoma (HL)in stages I-II without risk factors in most study groups. The complete remission rates achieved with this treatment strategy are more than 90%. However, the question arises, whether treatment intensity of chemotherapy, radiotherapy or both may be further reduced in these patients.

Aim: In the HD10 trial of the GHSG, reduction of ABVD cycles as well as reduction of IF- RT dose were investigated.

Methods: Patients were randomized between 4 cycles of ABVD followed by 30 Gy IF radiotherapy as standard treatment (arm A), 4 cycles ABVD + 20 Gy IF (arm B), 2 cycles ABVD + 30 Gy IF (arm C) and 2 cycles ABVD + 20 Gy IF (arm D).

Results: Between May 1998 and May 2002, 1131 HL patients with early stage disease (CS I,II without risk factors) were randomized. 847 patients (75%) were evaluable for this second interim analysis performed in August 2003. Patient characteristics were well balanced between the treatment arms. In total, 98.4% of the patients reached complete remission. Progressive disease or no change were observed in 0.9% of patients, relapse rate was 2.5%. In total, thirteen patients died during the study (1,5%). During chemotherapy there were 19% leukopenia as the most common WHO grade III/IV toxicity (4xABVD: 22 %, 2xABVD: 15%). Radiotherapy was well tolerated with dysphagia in 2.3%. Altogether ten secondary neoplasias were seen: 1AML, 4 NHL and 5 solid tumors.

After a median observation time of two years, overall survival (OS) and freedom from treatment failure (FFTF) rates were 98.5% and 96.6%, respectively. No statistical differences in FFTF and OS were detected between 4xABVD and 2xABVD. In addition, there was no statistical difference between the different doses of radiotherapy (30Gy vs. 20Gy).

Conclusions: Since only few events were observed, the results of this interim analysis can be interpreted as a trend that therapy intensity in combined modality treatment of early stage might be further reduced in terms of the number of chemotherapy cycles as well as the radiotherapy dose, even in IF-RT setting.