June 9, 2009 (Berlin, Germany) — A chemotherapy regimen of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbacine) was significantly better in terms of progression-free survival than the standard regimen of 4 cycles of ABVD in patients with early unfavorable Hodgkin's lymphoma (HL).
The finding, presented here at the 14th Congress of the European Hematology Association, comes from a study conducted in 1645 patients by the German Hodgkin Study Group (GHSG). The HD14 trial was terminated early, on the third interim analysis, because of the significantly better outcomes for patients treated with the hybrid regimen over ABVD (both were followed by 30 Gy involved-field radiotherapy [IF-RT]).
Patients in this study had early unfavorable HL — clinical stage 1 or 2 and risk factors, including large mediastinal mass, extranodal disease, high erythrocyte sedimentation rate, and 3 or more areas affected.
Currently, standard therapy for such patients is 4 cycles of ABVD followed by 30 Gy IF-RT. In this study, standard therapy was compared with 2 cycles of escalated BEACOPP plus 2 cycles of ABVD, similarly followed by 30 Gy IF-RT. The escalated BEACOPP regimen uses higher doses of some of the constituents, with granulocyte colony-stimulating factor support. The differences between escalated and usual BEACOPP are, respectively, 200 vs 100 mg/m2 for etoposide, 35 vs 25 mg/m2 for doxorubicin, and 1200 vs 650 mg/m2 for cyclophosphamide.
After 3 years, progression-free survival was seen in 97% of patients in the escalated BEACOPP group and 91% in the ABVD group. Freedom from treatment failure was 95% in the escalated BEACOPP group and 91% in the ABVD group.
A previous GHSG trial (GHSG HD11) that compared 4 cycles of ABVD with BEACOPP, followed by either 30 or 20 Gy IF-RT, showed no difference with respect to outcomes, and despite excellent initial remission rates, approximately 15% of patients with early unfavorable-stage HL relapsed within 5 years and another 5% suffered from progressive disease.
As a result, the researchers intensified treatment for early unfavorable HL in the HD14 trial. Patients in the escalated BEACOPP group showed a significant difference in terms of tumor control. "In a different study, we found a [progression-free survival] of 86% after 5 years of aggressive treatment in advanced-stage HL, so we reasoned that we should try this same regimen in early unfavorable-stage patients. HL is a highly curable disease, with 70% of patients achieving a cure over the long term, but there is still room for improvement in this particular group of patients with early unfavorable disease," study investigator Andreas Engert, MD, chair of GHSG and professor of internal medicine, Uniklinik Köln in Germany, told Medscape Oncology. Commenting on the study, Peter Johnson, MD, from the Cancer Research UK Centre at Southampton General Hospital, welcomed the findings but pointed out that many patients in this study had bulky disease and/or systemic (B) symptoms. In other countries, these patients would receive a full course of at least 6 cycles of chemotherapy, he said.
"It is an excellent and provocative study but it would be difficult to recommend adoption of the experimental arm of this study as the standard of care, particularly without an overall difference in survival. The information is clearly important and provides more support for the idea that treatment intensification can be effective in those patients with difficult disease, even at an early stage," Dr. Johnson added.
Now Aim to Reduce Toxicity
"It is still early on in the trial, so we need to look at longer-term follow-up, but we think we are near to the ceiling in terms of efficacy in these patients. A difference between the 2 groups of 6% of patients without progression at 3 years is clinically meaningful, but I think the aim now is to reduce toxicity," Dr. Engert pointed out.
Hematological adverse events were more common in the escalated BEACOPP group than in the ABVD group, including leukopenia (22% vs 81%), thrombocytopenia (<1%>). Study investigators are monitoring the effects of treatment on fertility.
Robert Pytlik, MD, a hematologist from Charles University General Hospital in Prague, Czech Republic, has treated several patients with the escalated BEACOPP regimen and found it is generally well tolerated. "We closely follow the GHSG and treat according to this. This is really an advance in unfavorable early HL and it shows that intensification at the earliest point is beneficial. I regard HL as an aggressive lymphoma, not indolent, so earliest possible intensification can improve results."
The majority (95%) of the study was funded Deutsche Krebshilfe (German Cancer Aid), and the remainder was funded by Amgen, Chugai, and Roche. Dr. Engert is chair of the GHSG. Dr. Johnson and Dr. Pytlik have disclosed no relevant financial relationships.
14th Congress of the European Hematology Association: Abstract 0553. Presented June 6, 2009.
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