A PHASE III STUDY OF RADIOTHERAPY OR ABVD PLUS RADIOTHERAPY VERSUS ABVD ALONE IN THE TREATMENT OF EARLY STAGE HODGKIN'S DISEASE
OBJECTIVES: I. Compare the 12-year survival of patients with clinical stage I-IIA Hodgkin's
disease treated with radiotherapy with or without doxorubicin, bleomycin, vinblastine, and
dacarbazine (ABVD) versus ABVD only. II. Compare the freedom from progression at 5 and 10
years in patients treated with these regimens. III. Compare the complete remission rate,
freedom from secondary disease progression at 5 and 10 years, and cause-specific survival at
5, 10, and 15 years in patients treated with these regimens. IV. Compare the short- and
long-term toxicity of these regimens in these patients. V. Compare the quality of life of
patients in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified by center.
Patients who are under age 40 and have lymphocyte-predominant or nodular sclerosing
histology, an erythrocyte sedimentation rate less than 50, and fewer than 4 disease sites
(supradiaphragmatic or pelvic node sites) are assigned to cohort 1 (good prognosis). All
other patients are assigned to cohort 2 (poor prognosis). Cohort 1: Arm I: Patients with
supradiaphragmatic disease undergo radiotherapy to the supradiaphragmatic lymph node areas
(mantle region), spleen, and para-aortic lymph nodes 5 days a week for 4 weeks. Patients
with pelvic disease undergo radiotherapy to an "inverted-Y" field (excluding the spleen) 5
days a week for 4 weeks. Arm II: Patients receive doxorubicin, bleomycin, vinblastine, and
dacarbazine IV on days 1 and 15 (ABVD). Treatment continues every 4 weeks for a total of 2
courses in the absence of disease progression or unacceptable toxicity. Patients with
complete remission (CR) after course 2 receive 2 additional courses past CR. Patients with
partial remission (PR) after course 2 receive 4 additional courses past PR. Patients with
unconfirmed/uncertain complete remission (CRu) receive 2-4 additional courses past CRu.
Cohort 2: Arm III: Patients receive ABVD as in arm II, followed 4-6 weeks later by
concurrent radiotherapy to the mantle region and upper abdomen to the level of L2 5 days a
week for 4 weeks. Alternatively, radiotherapy may also be administered sequentially to the
mantle region 5 days a week for 4 weeks and then to the upper abdomen to the level of L2 5
days a week for 4 weeks. Arm IV: Patients receive ABVD only as in arm II. Patients with
disease progression after treatment in arms II or IV are considered for radiotherapy.
Quality of life is assessed on day 1 of each course of chemotherapy (arms II-IV) and on day
28 of the last course of chemotherapy (arms II and IV); on the first and final days of
radiotherapy (arms I and III); at 4 weeks and at 3, 6, and 12 months after completion of
radiotherapy (arms I and III) or chemotherapy (arms II and IV); and then annually for 2-10
years. Patients are followed at months 3, 6, and 12 and then annually thereafter.
PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 7.5 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
12 year survival comparison
Ralph M. Meyer, MD, FRCPC
Margaret and Charles Juravinski Cancer Centre
Canada: Health Canada