西南肿瘤协作组S0008研究：高危黑色素瘤患者中高剂量干扰素α-2b与顺铂、长春花碱和达卡巴嗪加白细胞介素-2及干扰素的III期试验——癌症与白血病B组、儿童肿瘤协作组、东部肿瘤协作组和西南肿瘤协作组的一项组间研究
Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.
作者信息
Flaherty Lawrence E, Othus Megan, Atkins Michael B, Tuthill Ralph J, Thompson John A, Vetto John T, Haluska Frank G, Pappo Alberto S, Sosman Jeffrey A, Redman Bruce G, Moon James, Ribas Antoni, Kirkwood John M, Sondak Vernon K
机构信息
Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
出版信息
J Clin Oncol. 2014 Nov 20;32(33):3771-8. doi: 10.1200/JCO.2013.53.1590. Epub 2014 Oct 20.
PURPOSE
High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.
PATIENTS AND METHODS
S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).
RESULTS
In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.
CONCLUSION
Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
目的
高剂量干扰素（IFN）治疗1年（HDI）是美国食品药品监督管理局批准的高危黑色素瘤患者辅助治疗方案。改变IFN剂量和疗程的尝试并未提高疗效。我们试图确定疗程更短的生物化疗是否更有效。
患者与方法
S0008（S0008：化疗加生物治疗黑色素瘤患者）是一项组间III期试验，纳入高危患者（IIIA - N2a期至IIIC - N3期），随机分配他们接受HDI或由达卡巴嗪、顺铂、长春碱、白细胞介素 - 2、IFNα - 2b（IFN - α - 2b）和粒细胞集落刺激因子组成的生物化疗，每21天进行一个周期，共三个周期。共同主要终点为无复发生存期（RFS）和总生存期（OS）。
结果
总共纳入432例患者。3级和4级不良事件分别发生在57%的HDI患者和7%的生物化疗患者以及36%和40%的生物化疗患者中。中位随访7.2年时，生物化疗改善了RFS（风险比[HR]，0.75；95%置信区间，0.58至0.97；P = 0.015），生物化疗的中位RFS为4.0年（95%置信区间，1.9年至未达到[NR]），而HDI为1.9年（95%置信区间，1.2至2.8年），5年RFS分别为48%和39%。中位OS无差异（HR，0.98；95%置信区间，0.74至1.31；P = 0.55），生物化疗的中位OS为9.9年（95%置信区间，4.62年至NR），HDI为6.7年（95%置信区间，4.5年至NR），两组5年OS均为56%。
结论
生物化疗是高危黑色素瘤患者一种疗程更短的替代辅助治疗方法，与HDI相比，它在RFS方面有统计学意义的改善，但在OS方面无差异，且毒性更大。
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