BACKGROUND: Extended-field radiotherapy is effective in patients with early-stage Hodgkins disease, and more than 90% of these patients achieve a complete remission. However, up to 25% eventually relapse and have to be treated with intensive polychemotherapy. Low-dose neoadjuvant chemotherapy may reduce the risk of relapse and improve treatment results.
PATIENTS AND METHODS: A total of 640 patients with stage I or II Hodgkins disease without clinical risk factors (large mediastinal mass, massive spleen involvement, extranodal disease, elevated erythrocyte sedimentation rate, more than three lymph node areas) were enrolled in the HD7 trial and randomized as follows: Arm A received extended-field radiotherapy with 30 Gy, involved-field with 40 Gy, and spleen with 36 Gy; and arm B, two cycles of ABVD (Adriamycin, bleomycin(Drug information on bleomycin), vinblastine(Drug information on vinblastine), and dacarbazine(Drug information on dacarbazine)) followed by the same radiation therapy as in arm A. Both groups were well balanced for age, sex, histologic subtype, and stage.
RESULTS: The median follow-up time of this interim analysis, which is restricted to those patients randomized before December 1996, is 22 months. Of 407 patients, 365 were evaluable. The complete response (CR) rate was 96% in arm A and 98% in arm B (NS). Six patients (3%) progressed during therapy in arm A and one patient in arm B (P = .065).
Kaplan-Meier estimates of freedom from treatment failure showed a significant difference between arms A and B: 87% vs 96% at 24 months. The difference is mainly due to the reduced number of relapses in arm B (1 relapse vs 17 relapses in arm A). Survival rates are not different (97% vs 98% at 24 months). Of 12 deaths, 2 were due to Hodgkins disease and 3, to acute toxicity during radiotherapy. Two patients died during salvage therapy and one patient died from myelodysplastic syndrome/acute myelocytic leukemia [MDS/AML]).
Acute World Health Organization (WHO) grade 3/4 toxicities were rare (nausea, 8.6%; pharynx, 3.5%; esophagus, 3.3%; leukocytes, 2.9%). Nine patients developed secondary tumors, including one non-Hodgkin's lymphoma (NHL), one AML, and seven solid tumors.
CONCLUSION: The interim analysis demonstrates that neoadjuvant chemotherapy with two cycles of ABVD significantly reduces the rate of relapses and improves freedom from treatment failure. Current trials with combined-modality therapy aim to reduce acute and long-term toxicities by reduction of radiotherapy dose and volume