Purpose: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility.
Patients and methods: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment.
Results: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score <or= 2, nonbulky disease).
Conclusion: Apart from possibly in the best-prognosis group, where results are equivalent, ChlVPP/EVA hybrid produces significantly better FFP, EFS, and OS than VAPEC-B in patients with previously untreated Hodgkin's disease.