Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.
JAMA Oncol. 2022 Jul 1;8(7):1035-1041. doi: 10.1001/jamaoncol.2022.1968.
The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking.
To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL).
DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group.
Patients in each group were treated with the assigned regimen every 21 days for 6 cycles.
The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared.
Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%).
In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted.
ClinicalTrials.gov Identifier: NCT01501149.
基于 L-天冬酰胺酶的 SMILE（地塞米松、甲氨蝶呤、异环磷酰胺、L-天冬酰胺酶和依托泊苷）化疗方案在反应率和生存获益方面均优于含蒽环类药物的方案。然而，安全性并不理想。目前缺乏一种疗效确切且耐受性良好的方案。
比较 DDGP（地塞米松、顺铂、吉西他滨和培门冬酶）方案与 SMILE 方案在新诊断的晚期（III/IV 期）结外自然杀伤/T 细胞淋巴瘤（ENKL）患者中的疗效和安全性。
设计、地点和参与者：这是一项在中国 12 家参与医院进行的开放标签、多中心、随机临床试验，时间跨度为 2011 年 1 月至 2019 年 2 月。符合条件的患者为年龄在 14 至 70 岁、分期为 III/IV 期的新诊断的 ENKL 患者，且东部肿瘤协作组体力状态为 0 至 2 分。符合条件的患者被平均随机分配到 DDGP 或 SMILE 组。
两组患者均每 21 天接受一次治疗，共 6 个周期。
主要终点为无进展生存期（PFS），次要终点包括总缓解率和总生存期（OS）。比较 DDGP 和 SMILE 组之间的不良反应。
在 87 名随机患者中，80 名患者接受了治疗（DDGP 组 40 名，SMILE 组 40 名）；中位（IQR）年龄为 43（12）岁，51 名（64%）为男性。两组基线特征相似。中位随访 41.5 个月时，DDGP 组的中位 PFS未达到，而 SMILE 组为 6.8 个月（HR，0.42；95%CI，0.23-0.77；P=0.004），DDGP 组的中位 OS 未达到，而 SMILE 组为 75.2 个月（HR，0.41；95%CI，0.19-0.89，P=0.02）。DDGP 组的 3 年 PFS 率和 5 年 OS 率均高于 SMILE 组（3 年 PFS，56.6% vs 41.8%；5 年 OS，74.3% vs 51.7%）。DDGP 组的总缓解率高于 SMILE 组（90.0% vs 60.0%；P=0.002）。SMILE 组的 3 级和 4 级血液学毒性反应更为常见（白细胞减少症，85.0% vs 62.5%；中性粒细胞减少症，85.0% vs 65.0%）。
在这项随机临床试验中，DDGP 方案在新诊断的局部晚期 ENKL 患者中显示出了有前景的初步结果。需要更大规模人群的验证试验。
ClinicalTrials.gov 标识符：NCT01501149。
