Hutchinson R J, Fryer C J, Davis P C, Nachman J, Krailo M D, O'Brien R T, Collins R D, Whalen T, Reardon D, Trigg M E, Gilchrist G S
C.S. Mott Children's Hospital, Ann Arbor, MI, USA.
J Clin Oncol. 1998 Mar;16(3):897-906. doi: 10.1200/JCO.1998.16.3.897.
A randomized trial designed to compare mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and daccarbazine (ABVD) (regimen A) with ABVD plus low-dose regional (extended-field) radiation therapy (EF RT) (regimen B) for the treatment of children and adolescents with stages III and IV Hodgkin's disease was conducted by the Children's Cancer Group (CCG-521) from 1986 until 1990.
One hundred eleven eligible patients were randomized, 57 to regimen A and 54 to regimen B. All patients had pathologically verified stage III or stage IV Hodgkin's disease.
Overall survival (S) is 87% at 4 years and event-free survival (EFS) is 82%. Patients randomized to ABVD plus EF RT have a 4-year EFS of 87% compared with 77% for patients randomized to MOPP/ABVD (P = .09, two-sided). Patients randomized to ABVD plus EF RT have a 4-year S of 90% compared with 84% for patients randomized to MOPP/ABVD (P = .45, two-sided). Significant prognostic factors in multivariate analysis for EFS are stage of disease, erythrocyte sedimentation rate (ESR) at diagnosis, liver size at diagnosis, and, among stage III patients, the size of the mediastinal mass at diagnosis. The acute toxicities of treatment are largely hematopoietic in nature, whereas acute pulmonary and cardiac toxicities are modest and not limiting.
The results of this study show that, in advanced-stage Hodgkin's disease in children, equivalent results can be obtained by the addition of either MOPP or low-dose EF RT to the ABVD regimen; whether the addition of either contributes to outcome was not addressed in this study and will require additional testing. It is clear, however, that MOPP chemotherapy can safely be eliminated from front-line combination chemotherapy regimens for advanced Hodgkin's disease in pediatric patients.
儿童癌症组(CCG - 521)于1986年至1990年开展了一项随机试验,旨在比较氮芥、长春新碱、丙卡巴肼和泼尼松(MOPP)/阿霉素、博来霉素、长春花碱和达卡巴嗪(ABVD)(方案A)与ABVD加低剂量区域(扩大野)放射治疗(EF RT)(方案B)治疗Ⅲ期和Ⅳ期霍奇金病儿童及青少年的效果。
111例符合条件的患者被随机分组,57例接受方案A,54例接受方案B。所有患者均经病理证实为Ⅲ期或Ⅳ期霍奇金病。
4年总生存率(S)为87%,无事件生存率(EFS)为82%。随机接受ABVD加EF RT的患者4年EFS为87%,而随机接受MOPP/ABVD的患者为77%(双侧P = 0.09)。随机接受ABVD加EF RT的患者4年S为90%,而随机接受MOPP/ABVD的患者为84%(双侧P = 0.45)。多因素分析中EFS的显著预后因素包括疾病分期、诊断时的红细胞沉降率(ESR)、诊断时的肝脏大小,以及Ⅲ期患者中诊断时纵隔肿块的大小。治疗的急性毒性主要为血液学毒性,而急性肺部和心脏毒性较轻且不构成限制。
本研究结果表明,在儿童晚期霍奇金病中,ABVD方案加用MOPP或低剂量EF RT均可获得相似结果;本研究未探讨二者加用是否对预后有影响,这需要进一步试验。然而,很明显,MOPP化疗可安全地从儿童晚期霍奇金病的一线联合化疗方案中去除。