New Standard in Early-Stage Hodgkin's Lymphoma

Zosia Chustecka

December 21, 2009

December 21, 2009 (New Orleans, Louisiana) — A new standard of care for the treatment of early-stage Hodgkin's lymphoma has now been established. The final results from a large German study presented here at the American Society of Hematology 51st Annual Meeting show that the best results were seen with a combination of chemotherapy and radiation.

Two cycles of chemotherapy with ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) followed by 20 Gy involved-field radiotherapy (IFR) is the new standard of care for patients with Hodgkin's lymphoma in early favorable stages, concluded lead researcher Andreas Engert, MD, from the University of Cologne, Germany.

In the discussion period following his presentation, several experts congratulated him and agreed that this should be the new standard of care. In an interview with Medscape Oncology, Richard Van Etten MD, PhD, director of the Cancer Center at Tufts Medical Center, in Boston, Massachusetts, explained that there was a long-standing question about the treatment of these patients with favorable early-stage disease, and this trial has finally offered an answer as to what is the best option.

Ongoing Debate About Best Approach

In the ongoing debate about the best approach to the treatment of patients with early favorable Hodgkin's lymphoma, one of the main questions has been whether to use chemotherapy alone or chemotherapy in combination with radiation, but there have also been questions about the optimum radiation dose and about the optimal number of chemotherapy cycles, Dr. Engert explained.

The German Hodgkin Study Group addressed these questions in a large trial, conducted in 1370 patients, which had 4 treatment groups. Each group had a different combination of chemotherapy with ABVD (2 or 4 cycles) and IFR (20 Gy or 30 Gy).

The 4 treatment groups were: 4 cycles of ABVD plus 30 Gy IFR; 4 cycles of ABVD plus 20 Gy IFR; 2 cycles of ABVD plus 30 Gy IFR; and 2 cycles of ABVD plus 20 Gy IFR.

All of the groups showed a similar efficacy, but there were significant differences in toxicity, Dr. Engert told the meeting.

Complete remission was achieved in 97% of patients who were treated with either 4 or 2 cycles of ABVD and who received 20 Gy IFR, and in 99% of patients who received 30 Gy.

With a median follow-up of 79 to 91 months, there was no significant difference between 4 and 2 cycles of chemotherapy in terms of overall survival at 5 years (97.1% with 4 cycles of ABVD and 96.6% with 2 cycles), in freedom from treatment failure (93% vs 91.1%), or in progression-free survival (3.5% vs 91.2%).

There were also no significant differences between the 2 doses of radiotherapy in terms of overall survival at 5 years (97.6% with 30 Gy and 97.5% with 20 Gy), in freedom from treatment failure (93.4% vs 92.9%), or progression-free survival (93.7% vs 93.2%).

"Importantly, there were also no significant differences in overall survival, freedom from treatment failure, or progression-free survival when all 4 arms were compared," Dr. Engert explained.

However, there were significant differences in toxicity, Dr. Engert reported. Four cycles of ABVD were significantly more toxic than 2 cycles. Overall adverse events were reported in 52% of patients receiving 4 cycles and in 33% receiving 2 cycles; leukopenia was seen in 24% and 15%, respectively, and alopecia was seen in 28% and 15%, respectively.

A similar pattern was seen with radiotherapy, with more toxicity at the higher dose. Overall adverse events were reported in 8.2% of patients treated with 30 Gy and in 2.9% treated with 20 Gy, dysphagia was seen in 3% and 2%, respectively, and mucositis was seen in 3.4% and 0.7%, respectively.

Dr. Engert concluded that because all of the treatment groups showed a similar efficacy, the new standard of care should be the least toxic treatment of 2 cycles of ABVD and 20 Gy IFR.

Dr. Engert also said that his group is continuing with this research and is looking at whether the radiotherapy portion of the treatment is necessary. A new trial will compare 2 cycles of ABVD with and without the addition of 20 Gy IFR. In addition, an ongoing study is looking at the various components of the chemotherapy regimen to see if any drug can be dropped, he said. This trial is comparing ABVD with ABV, AVD, and AV, he added.

The researchers have disclosed no relevant financial relationships.

American Society of Hematology (ASH) 51st Annual Meeting: Abstract 716. Presented December 7, 2009.

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