POG 8625: A Randomized Trial Comparing Chemotherapy With Chemoradiotherapy for Children and Adolescents With Stages I, IIA, IIIA1 Hodgkin Disease

Abstract

To determine if 6 courses of chemotherapy alone could achieve the same or better outcome than 4 courses of chemotherapy followed by radiation therapy (chemoradiotherapy) in pediatric and adolescent patients with Hodgkin disease. Children < or =21 years old with biopsy-proven, pathologically staged I, IIA, or IIIA1 Hodgkin disease were randomly assigned 6 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine (treatment 1) or 4 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine +2550 cGy involved-field radiotherapy (treatment 2). The complete response rate was 89%, with a complete response and partial response rate of 99.4%. There was no statistically significant difference in event-free survival (EFS) or overall survival between arms. The EFS for those who achieved an early complete response was significantly higher than for those who did not. For pediatric patients with asymptomatic low-stage and intermediate-stage Hodgkin disease, chemotherapy and chemoradiotherapy both resulted in 3-year EFS of approximately 90% and statistically indistinguishable 8-year EFS and overall survival, without significant long-term toxicity. Early response to therapy was associated with higher EFS, a concept that has led to the Children's Oncology Group paradigm of response-based risk-adapted therapy for pediatric Hodgkin disease.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

“…29 However, these are minor points, as the direction of the effect is clear and only the magnitude may vary slightly. Again, the trials included in the sensitivity analyses 20,[34][35][36][37][38] also supported the results in favor of CMT. Three trials had effect estimates favoring CMT, two trials observed no deaths 34,36 and only one trial 20 observed a slight effect favoring chemotherapy alone, which was not statistically significant.…”

“…20,[34][35][36][37][38] When including all of these trials into a meta-analysis for tumor control, the HR was 0.38 (95% CI 0.28 to 0.51). When restricting the analysis to the trials that kept the number of cycles the same between the group that received radiotherapy and those that did not [34][35][36][37] the HR was 0.39 (95% CI 0.27 to 0.55).…”

“…The two trials that examined chemotherapy plus radiotherapy versus more chemotherapy reported conflicting results among the two trials. 20,38 The trial by Meyer and colleagues 20 comparing four cycles of ABVD plus subtotal nodal irradiation with six cycles of ABVD had an (estimated) HR of 1.73 Combined modality treatment (CMT) haematologica | 2010; 95 (3) 497 Table 2. Definitions of tumor control.…”

“…38 The quality of the trials in the main analysis was acceptable. Randomization procedures were not reported in four of the five trials;…”

“…37 Finally, two trials were identified in which the patients in the chemotherapy alone group received more cycles of chemotherapy than the patients in the chemotherapy plus radiotherapy group. 20,38 Characteristics and main results of these trials are described in the Online Supplementary Table S1.…”