Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.
PURPOSE To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.