University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
J Clin Oncol. 2011 Nov 10;29(32):4234-42. doi: 10.1200/JCO.2010.33.9549. Epub 2011 Oct 11.
Eight cycles of BEACOPP(escalated) (escalated dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by radiotherapy (RT) to initial bulk or residual tumor mass is the German Hodgkin Study Group standard of care for advanced-stage Hodgkin's lymphoma (HL). However, treatment-related toxicity is a concern, and the role of RT in this setting is unclear. The HD12 study thus aimed to reduce toxicity while maintaining efficacy.
In this prospectively randomized multicenter trial, eight cycles of BEACOPP(escalated) was compared with four cycles of BEACOPP(escalated) followed by four cycles of the baseline dose of BEACOPP (BEACOPP(baseline); 4 + 4), and RT with no RT in the case of initial bulk or residual disease. The study was designed to exclude a difference in 5-year freedom from treatment failure (FFTF) rate of 6%.
Between January 1999 and January 2003, 1,670 patients age 16 to 65 years were enrolled onto the HD12 study. At 5 years, FFTF was 86.4% in the BEACOPP(escalated) arm and 84.8% in the 4 + 4 arm (difference, -1.6%; 95% CI, -5.2% to 1.9%), and overall survival was 92% versus 90.3% (difference, -1.7%; 95% CI, -4.6% to 1.1%). Deaths related to acute toxicity of chemotherapy were observed in 2.9% of patients (BEACOPP(escalated), n = 19; 4 + 4, n = 27). FFTF was inferior without RT (90.4% v 87%; difference, -3.4%; 95% CI, -6.6% to -0.1%), particularly in patients who had residual disease after chemotherapy (difference, -5.8%; 95% CI, -10.7% to -1.0%), but not in patients with bulk in complete response after chemotherapy (difference, -1.1%; 95% CI, -6.2% to 4%).
The reduction of BEACOPP to the 4 + 4 regimen did not substantially reduce severe toxicity but might decrease efficacy. Our results do not support the omission of consolidation RT for patients with residual disease. Alternative strategies for improving the risk-to-benefit ratio for patients with advanced HL are needed.
在初始大块或残留肿瘤中，使用 8 个周期的 BEACOPP（ escalated ）（博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、丙卡巴肼和泼尼松的递增剂量）联合放疗（RT ）是德国 Hodgkin 研究组治疗晚期霍奇金淋巴瘤（HL ）的标准治疗方法。然而，治疗相关的毒性是一个关注点，而且在这种情况下 RT 的作用尚不清楚。因此，HD12 研究旨在降低毒性的同时保持疗效。
在这项前瞻性随机多中心试验中，比较了 8 个周期的 BEACOPP（ escalated ）与 4 个周期的 BEACOPP（ escalated ）后紧接着 4 个周期的基线剂量 BEACOPP（ BEACOPP（ baseline ）），以及初始大块或残留疾病时有无 RT 的情况。该研究旨在排除 5 年无治疗失败（ FFTF ）率相差 6%的可能性。
1999 年 1 月至 2003 年 1 月期间，共有 1670 名年龄在 16 至 65 岁之间的患者入组 HD12 研究。5 年时，BEACOPP（ escalated ）组的 FFTF 为 86.4%，4+4 组为 84.8%（差异，-1.6%；95%CI，-5.2%至 1.9%），总生存率为 92%对 90.3%（差异，-1.7%；95%CI，-4.6%至 1.1%）。化疗相关急性毒性死亡的患者占 2.9%（BEACOPP（ escalated ），n=19；4+4，n=27）。无 RT 时 FFTF 较差（90.4%对 87%；差异，-3.4%；95%CI，-6.6%至-0.1%），尤其是化疗后残留疾病患者（差异，-5.8%；95%CI，-10.7%至-1.0%），但化疗后大块完全缓解的患者无此差异（差异，-1.1%；95%CI，-6.2%至 4%）。
将 BEACOPP 减少到 4+4 方案并没有显著降低严重毒性，但可能降低疗效。我们的结果不支持对残留疾病患者省略巩固性 RT 。需要有改善晚期 HL 患者风险效益比的替代策略。
