Background: Combined modality treatment consisting of chemotherapy (CT) followed by involved field radiotherapy (IF-RT) is the standard treatment for intermediate stage (early unfavourable) Hodgkin′s lymphoma (HL). Despite high complete remission (CR) rates comparable to early favorable stage HL, failure rates are remarkably higher in this group of patients.

Aim: In the HD 11 multicenter trial of the GHSG, introduction of the BEACOPP regimen for intensification of chemotherapy in combination with dose reduction of IF-RT on 20 Gy was tested in an attempt to improve therapy outcome.

Methods: Between May 1998 and July 2002, 1363 patients aged 16–75 suffering from intermediate stage HL (CS I, IIA with risk factors or IIB with elevated ESR and/or 3 3 nodal areas) were randomised according to a factorial design between: 4 cycles of ABVD followed by 30 Gy IF-RT (arm A - standard treatment), 4 ABVD + 20 Gy IF-RT (arm B), 4 BEACOPP basis + 30 Gy IF-RT (arm C) and 4 BEACOPP basis + 20 Gy IF-RT (arm D).

Results: In the fourth interim analysis in August 2003, 1047 (77%) patients were evaluable for chemotherapy and 982 (72%) for radiotherapy evaluation. Patient characteristics were well balanced between the treatment arms in regard to age, gender, clinical stage, histopathology and performance status. 95.1% patients reached CR, 2.0% suffered progression, the relapse rate was 5.9%, the mortality rate 3.2%. The most frequent haematological toxicity was leucopenia observed in 33% of patients (ABVD: 27%, BEACOPP: 40%). Infection rate was 5% (ABVD: 4%, BEACOPP:7%). The most frequent toxicity during radiotherapy was dysphagia in 5.6%. Nine secondary neoplasias were observed: 2 AML, 3NHL, 4 solid tumors.

After a median observation time of two years overall survival (OS) was 97.4% (95%-CI: 96-98) and freedom from treatment failure (FFTF) was 89.9% (95%-CI: 88-92). Both for FFTF and OS, there was no sequential significant difference either between ABVD and BEACOPP arms nor between 30 Gy and 20 Gy IF-RT arms.

Conclusions: At two years of median observation time, no differences in treatment outcome were detected either between chemotherapy regimes nor between the different doses of radiotherapy. The low FFTF (89,9 % at two years) led us to further intensification of treatment by the introduction of 2 cycles of escalated BEACOPP + 2 cycles ABVD +30 Gy IF-RT in the next study generation (HD14 study).

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