Trials in advanced Hodgkin's disease: asking the right questions at the right time
The treatment of advanced Hodgkin’s disease poses unique lenges for those involved in the design of randomized clin trials. The disease predominantly affects young adults, app imately 70% of whom are likely to be cured by modern f line combination chemotherapy (Canellos et al, 1992). Late effects of treatment, particularly gonadal toxicity and the risk secondary myelodysplasia and acute myeloid leukaemia (M AML), are major issues for long-term survivors. In view of the high response and cure rates, randomized tria this disease must recruit large numbers of patients to adequate statistical power. Attempts to improve response survival rates by intensifying initial chemotherapy must balanced against the potential for long-term toxicity. In view of effectiveness of salvage therapy, particularly high-dose the and autologous stem cell transplantation (ASCT) (Linch e 1993; Sweetenham et al, 1997; Yuen et al, 1997; Lazarus 1999) intensified initial therapy may only be appropriate patients with adverse prognostic factors at presentation. The stakes are high for a young adult with advanced Hodg disease. When asked to participate in a clinical trial, the pa must be reassured that this trial is asking a relevant question his or her chances of long-term survival will not be comprom by participating in the trial, and that the potential long-term c sequences of the treatment will be addressed. The resu the British National Lymphoma Investigation (BNLI)/Centr Lymphoma Group (CLG) randomized trial reported in this issu the British Journal of Cancer(Hancock et al, 2001) should b judged against these criteria. This study was initiated in 199 about the same time that Cancer and Leukemia Group B (CAL reported the results of a randomized trial comparing AB (doxorubicin, bleomycin, vinblastine, dacarbazine), MO (mustine, vincristine, procarbazine, prednisone), and altern MOPP/ABVD in 361 patients (Canellos et al, 1992). Respo failure-free and overall-survival rates were equivalent for AB and MOPP/ABVD. Both were superior to MOPP alone. Since publication of this study, ABVD has been widely regarded ‘standard’ chemotherapy for advanced Hodgkin’s disease. The BNLI/CLG trial compared an alternating ‘variant’ MOPP/ABVD, known as ChlVPP/PABIOE (chlorambucil, vi blastine, procarbazine, prednisone/prednisone, doxorubicin, mycin, vincristine, etoposide) with PABIOE alone. The origi phase II multicentre trial of the ChlVPP/PABIOE regimen p radiotherapy reported 5 year FFS and OS rates of 68% and respectively (Cullen et al, 1994). These results are comparab MOPP/ABVD. The authors’ rationale for a randomized comparison of regimen with PABIOE alone was 2-fold. Firstly, the CALGB stu was relatively small and lacked sufficient power to conf halal xt ef S/