Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin's Disease

Abstract

This multicentric randomized study was a phase III trial that aimed to assess and compare the efficacy and toxicity of COPP-ABVD with standard and increased dose BEACOPP regimen. From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage 1MB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine, (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), or increased-dose BEACOPP, along with growth factor support, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparisonof the COPP-ABVD group with the BEACOPP group and P less than 0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent and 91 percent, respectively (P=O.I6 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BRACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. The incidence of acute hematological effects was similar in the COPP-ABVD and standard BEACOPP groups but wassignificantly increased in the increased dose BEACOPP group. In this group grade 3 and 4 Icukopenia was common in all 8 cycles whereas the frequency of thrombocytopenia and anemia increased in the last 4 cycles. Grade 3 and 4 infections occurred in a higher proportion of patients in this group. The incidence of fatal acute treatment related effects were similar in all groups (less than 2 percent). The median duration of chemotherapy from the first to the last day of drug administration was weeks in the COPPABVD group (planned, 30 weeks), weeks in the BEACOPP group (planned, 23 weeks), and 27.7 weeks in the increased dose BEACOPP group (planned, 23 weeks) The percentage of patients who received radiotherapy was 64 percent in the COPP-ABVD group and 71 percent in the other two groups. Patients were divided into three subgroups based on the International prognostic index (IPI) within each prognostic subgroup standard and increased dose BEACOPP resulted in lower rates of early progression and five-year freedom from treatment failure. All age groups seemed to benefit from the standard and increased dose BEACOPP, with the possible exception of those who were 60 to 65 years of age. The actuarial rate of secondary acute leukemia five years after diagnosis of Hodgkin's disease was 0.4 percent in the COPP-ABVD group (n=l), 0.6 percent in the BEACOPP group (n=4) and 2.5 percent in the increased dose BEACOPP group (n=9). Solid tumors were recorded in three, eight and two patients, respectively and second non-Hodgkin's lymphoma in seven, four and five patients, respectively