The final 5-year analysis of the four-arm HD11 multicenter randomized clinical trial reveals that four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) plus 30-Gy involved-field radiotherapy (IFRT) is the treatment of choice for patients with early unfavorable Hodgkin lymphoma, according to a presentation by the German Hodgkin Study Group at the plenary session of the 52nd Annual Meeting of the American Society for Radiation Oncology (ASTRO), held October 31-November 4 in San Diego.1

Study Specifics

In the European trial, 1,395 patients with early, intermediate-stage Hodgkin lymphoma from 328 medical centers and five countries received a regimen of 4 × ABVD plus 20- or 30-Gy IFRT; or 4 × BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus 20- or 30-Gy IFRT. Results revealed that while patients who received the more intensive chemotherapy and radiotherapy regimens more often suffered grade 3 or 4 toxicity, the efficacy of the standard 4 × ABVD plus 30-Gy IFRT regimen was equivalent to that of both 4 × BEACOPP regimens.

Overall, the complete remission rate was 94.1%, and the freedom from treatment failure rate was 85% in the trial-and those complete remission and freedom from treatment failure rates did not differ among the two BEACOPP regimens and the 4 × ABVD plus 30-Gy IFRT arm. However, four cycles of ABVD followed by 20-Gy IFRT was inferior to the other three arms, with a 5-year freedom from treatment failure difference of 5.7% (P = .052).

"Our study shows that four cycles of ABVD chemotherapy plus 30-Gy involved-field radiotherapy remains the standard treatment for early unfavorable Hodgkin lymphoma," said Hans Theodor Eich, MD, PhD, lead author of the study and a radiation oncologist at the University of Cologne, Germany. "Prior to the study, it was unclear what the optimal chemotherapy regimen and the most effective dose of radiation was," he added.

Acute Toxicities

Compared with early favorable disease, the outcome in early unfavorable Hodgkin lymphoma-with up to 80% long-term tumor control-still leaves room for improvement, the authors of the trial said. Thus, HD11 was begun with the aim of optimizing patient outcomes.

With a median follow-up of 91 months, 105 patients in the HD11 trial had died. The most frequent events were Hodgkin lymphoma, secondary neoplasias, and cardiovascular mortality. The investigators found no difference in overall survival among the four treatments or modalities. However, acute toxicities varied according to treatment regimen. Compared to those who received ABVD, more patients treated with BEACOPP developed grade 3/4 toxicity (51.5% vs 73.8%, P < .001).

The most common side effects were hematologic toxicities such as leukopenia and hair loss. Acute toxicities were also more frequent among patients who received 30-Gy radiotherapy than among those who were treated with 20 Gy (12% vs 5.7%, P < .001). The most common toxicities during radiotherapy were dysphagia and mucositis.
The authors' final conclusions included a recommendation that IFRT dose should be reduced to 20 Gy in patients with early unfavorable Hodgkin lymphoma only if accompanied by intensified chemotherapy. They also noted that 4 × ABVD plus 30-Gy IFRT should remain the standard treatment for these patients outside of clinical trials. ■

Reference

1. Eich HT, Mueller RP, Diehl V, et al: Intensified chemotherapy and dose-reduced involved field radiotherapy in patients with early unfavorable Hodgkin lymphoma: Final analysis of the German Hodgkin Study Group (GHSG) randomized HD11 trial. 52nd ASTRO Annual Meeting. Abstract 2. Presented November 1, 2010.