Abstract
Background The ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) is widely accepted as standard treatment for patients with advanced HL. There are potential long term cardiac and pulmonary toxicites, particularly in combination with mediastinal radiotherapy. The SV regimen comprises brief duration combination chemotherapy, with relatively low cumulative doses of alkylating agents, doxorubicin and bleomycin, followed by consolidation radiotherapy to sites of bulk disease. High response and disease free survival rates are reported in single institution and multi-centre phase II studies. This randomized phase II trial comparing SV with ABVD was designed to determine 1) the feasibility of the SV regimen; 2) response rate compared with ABVD; and 3) acute toxicity of SV.
Methods Patients with previously untreated advanced HL were randomised to receive SV chemotherapy for 12 weeks or 6 to 8 cycles of ABVD. All patients with bulky disease (mediastinal disease > 1/3 of CTR, nodal masses >5cm, macroscopic splenic nodules on CT scan) received involved field radiotherapy (IFRT). ABVD (days 1 & 15: doxorubicin 25mg/m2, bleomycin 10units/m2, vinblastine 6mg/m2, dacarbazine 375mg/m2), q28. SV (mustine 6mg/m2, wks 1,5,9, doxorubicin 25mg/m2, wks 1,3,5,7,9,11, vinblastine 6mg/m2 wks 1,3,5,7,9,11, prednisone 40mg/m2 alternate days, vincristine 1.4mg/m2 wks 2,4,6,8,10,12, bleomycin 5iu/m2 wks 2,4,6,8,10, 12, etoposide 60 mg/m2 wks 3,7,11).
Results From Mar 1998 to Jan 2002, 150 (74 SV, 76 ABVD) patients were randomised from 15 UK centers. Pre-treatment characteristics were balanced between the two groups: median (range) age 33 (18–67), male 57%, stage II 43%, III 27%, IV 29%, 76% with B symptoms. 97% SV patients completed 12 weeks treatment, 88% patients received 6 or more cycles of ABVD. In both groups, 75% patients received IFRT. Grade 3 or 4 toxicity was rare. 49% SV and 79% ABVD patients required G-CSF. Overall response rate was 86% in SV and 88% in ABVD. With median follow-up of 42 months, 2-year overall survival was 95%, (95% CI=92%–98%). No treatment related death occurred.
Conclusion Stanford V is a potentially less toxic alternative to ABVD. Phase III trial evaluation is underway in the UK.
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