In 1992 the German Hodgkin Study Group (GHSG) designed the BEACOPP regimen in an effort to increase the number of patients with advanced Hodgkin Lymphoma (HL) cured with first-line chemotherapy.
After dose-finding and feasibility studies, the GHSG designed a 3-arm study, the HD9 trial, comparing COPP/ABVD, standard BEACOPP and escalated BEACOPP in patients with advanced HL. Radiotherapy was prescribed for bulky disease at diagnosis (30Gy) or for residual disease (40Gy) after 8 cycles of chemotherapy and about two thirds of patients received consolidation radiotherapy. In the final analysis, 1201 patients were evaluated. There was a significant superiority over the COPP/ABVD arm for freedom from treatment failure at 5 years with 87% for escalated BEACOPP versus BEACOPP baseline (76%) and COPP/ABVD (69%), a highly significant result. A major difference was also observed in the rate of primary progressive disease during initial therapy, which was significantly lower with escalated BEACOPP (2%) versus BEACOPP baseline (8%) and COPP/ABVD (12%) (p < 0.001). The OS rates for COPP/ABVD were 83%, for BEACOPP baseline were 88% and for escalated BEACOPP 91%, a highly significant survival difference (p < 0.002). However, escalated BEACOPP was associated with greater haematological toxicity and a greater need for red cell and platelet transfusions. Second malignancies, including AML possibly related to etoposide, occurred in all three treatment arms, particularly with escalated BEACOPP, with escalated BEACOPP (n = 9 AML/MDS), baseline BEACOPP (n = 4 AML/MDS) and COPP/ABVD (n = 1 AML/MDS). However, the total rate of secondary malignancies was highest in the COPP/ABVD arm with 4.2% compared to 3.4% in the escalated BEACOPP arm. The death rates at 5 years, including all acute and late causes of death, were 18.8% in the COPP/ABVD arm (49/260), 13% in the baseline BEACOPP arm (61/469) and 8.6% in the escalated BEACOPP arm (40/460). That meant that 10 more patients out of 100 died in the COPP/ABVD arm.r
Importantly, a further study comparing standard BEACOPP and COPP/ABVD in patients aged 66-75 found no significant differences between these regimens in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTR) (46%) at 5 years.r
After establishing that escalated BEACOPP was more effective than COPP/ABVD for the treatment of advanced HL in patients under the age of 65 the GHSG then examined whether a 14-day variant of standard BEACOPP (achieving dose intensity through increasing dose density) would have the clinical benefits of escalated BEACOPP but would have reduced toxicity and less risk of secondary AML/MDS.r
The GHSH tested the feasibility, toxicity and efficacy of BEACOPP-14 in 99 patients with stage IIB with LMM/extranodal disease (23%) and stage III/IV (77%) in a multicentre pilot study involving 32 centres. The final analysis with 94 evaluable patients was performed in August 2002.r 91% of the 94 patients received 8 cycles, 77% were given within 16 days, and 94% were given within 22 days. Seventy percent of the patients received consolidation radiotherapy. 88 patients (94%) achieved a CR and only 4 had progressive disease. With a median follow-up of 34 months, 5 patients relapsed, 1 developed high-grade NHL and 3 patients died (1 due to toxicity and 2 due to progressive disease). The estimated FFTF was 90% and the OS 97% at 34 months median observation time. Acute haematological toxicity was moderate, ranging between that of the escalated and the standard BEACOPP-21 regimens, with 75% of patients experiencing WHO grade 3 or 4 leukopenia, 23% thrombocytopenia and 65% anaemia.
On the basis of these results the GHSG is currently comparing BEACOPP-14 with escalated BEACOPP in a prospective, multicentre randomized trial. Other large intergroup studies comparing ABVD versus BEACOPP (EORTC 20012) and ABVD versus Stanford V (E2496).
Outcome of treatment and five year survival rates:r
© N Engl j Med 2003
Outcome by International Prognostic Index:r
© N Engl j Med 2003
Acute adverse effects of chemotherapy:r
© N Engl j Med 2003
Acute hematological toxicity of BEACOPP-14 compared with BEACOPP-21 (baseline and escalated):r
© Journal of Clinical Oncology 2003