DENVER-Among patients with early-stage Hodgkin's disease (HD) without adverse features, outcomes with combined modality regimens are still very good when chemotherapy is reduced by half or radiation therapy is reduced by a third, according to interim results of a randomized trial. Rolf P. Müller, MD, head of the Department of Radiation Oncology at the University of Cologne, Germany, presented the study findings at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 2).
The study-the German Hodgkin's Study Group HD-10 trial-expanded on the results of the group's preceding trials and on other studies testing combined-modality treatment and the feasibility of reducing treatment intensity, Dr. Müller explained. The group's HD-7 trial in patients with early-stage Hodgkin's disease showed good efficacy with less intense chemotherapy in combination with radiation therapy, and the HD-8 trial in patients with early but unfavorable disease showed that 30 Gy of radiation therapy worked as well when delivered to the involved field as when delivered to the extended field. "But still," he noted, "the optimal chemotherapy regimen and the number of cycles were not clear, and the optimal radiotherapy dose has also not been fixed."
The new trial enrolled patients who had clinical stage I or II Hodgkin's disease without adverse features (a large mediastinal mass, extranodal disease, high erythrocyte sedimentation rate, or three or more lymph node areas involved). The patients were randomized in a 2-by-2 factorial design to chemotherapy-either two or four cycles of ABVD (Adriamycin, bleomycin(Drug information on bleomycin), vinblastine(Drug information on vinblastine), and dacarbazine(Drug information on dacarbazine))-and then to involved-field radiation therapy-either 20 Gy or 30 Gy.
Interim Analysis
The interim analysis included 1,107 patients who had a median follow-up of 41 months. With respect to chemotherapy toxicity, patients receiving four cycles of ABVD had higher incidences of WHO grade 3 or 4 toxicities than their counterparts receiving only two cycles; differences were significant for leukopenia, hair loss, and infection, Dr. Müller said. With respect to radiation therapy toxicity, the incidence of WHO grade 3 or 4 toxicity was low overall (3%) and mainly accounted for by dysphagia and mucositis.
Second cancers occurred in 23 patients (about 2%), with no difference by treatment group. The second cancers were AML (2 patients, 9% of these cancers), non-Hodgkin's lymphoma (14 patients, 61%), and solid tumors (7 patients, 30%).
According to Dr. Müller, rates of adherence to the two chemotherapy protocols were similar, as were rates of adherence to the two radiation therapy protocols. Three months after chemotherapy, almost 98% of the patients had a complete remission or a complete remission with residual changes (less than 1.5 cm mass on imaging); 3 months after radiation therapy, the percentage was 99%.
Overall, 2.4% of patients have died, Dr. Müller noted. The leading causes of death were Hodgkin's disease (22% of deaths), toxicity of the primary chemotherapy (22%), secondary cancers (15%), and toxicity of the salvage chemotherapy regimen (11%).
For the entire study population, at 4 years, the rate of freedom from treatment failure (the primary endpoint) was 94%. It did not differ for patients receiving two or four cycles of chemotherapy (93% and 94%, respectively) or for patients receiving 20 or 30 Gy of radiation therapy (93% and 94%).
At 4 years, the rate of overall survival was 97% for the whole study population. It did not differ for patients receiving two or four cycles of chemotherapy (98% and 99%, respectively) or for patients receiving 20 or 30 Gy of radiation therapy (98% and 97%).
"Based on the results of HD-7 and HD-8, we can state that combined-modality treatment is a standard, and HD-10 shows no significant difference in freedom from treatment failure and overall survival between the treatment arms-neither for chemotherapy nor for radiation therapy," Dr. Müller concluded.
He added that the ongoing HD-13 trial is testing the feasibility of further reducing the intensity of chemotherapy, with patients receiving two cycles of ABVD, ABV, AVD, or AV, each followed by 30 Gy of involved-field radiotherapy.
