剂量递增可使转移性肾细胞癌患者的舒尼替尼治疗潜力最大化。
Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma.
机构信息
Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary.
Institute of Radiotherapy and Clinical Oncology, Borsod County Hospital and University Academic Hospital, Szentpéteri Kapu 72-76, Miskolc, H-3526, Hungary.
出版信息
BMC Cancer. 2018 Mar 15;18(1):296. doi: 10.1186/s12885-018-4209-9.
BACKGROUND
In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study.
METHODS
From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively.
RESULTS
The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%.
CONCLUSIONS
Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.
背景
在转移性肾细胞癌患者中，基于有限的证据，增加舒尼替尼的暴露与更好的结果相关。本研究分析了接受个体化剂量递增舒尼替尼治疗与标准治疗相比的患者的生存和毒性数据。
方法
自 2013 年 7 月起，对根据 RECIST 1.1 标准出现轻微进展但仍为稳定疾病的转移性肾细胞癌患者，采用递增剂量舒尼替尼（第一级：4/2 或 2×2/1 方案为 62.5mg/天，第二级：4/2 或 2×2/1 方案为 75mg/天）进行治疗。前瞻性收集了这些患者的数据。关于特征、结果和毒性数据，对登记册进行了探索性回顾性分析，比较了 2013 年 7 月 1 日之前和之后（递增剂量组）和对照组（标准剂量组）的治疗。
结果
本研究共纳入 103 例接受舒尼替尼治疗的患者，中位总生存期和无进展生存期分别为 25.36±2.62 个月和 14.2±3.22 个月。其中 48.5%的患者出现轻微进展。第一级和第二级剂量递增分别在 18.2%和 4.1%的患者中显示。22.2%的患者改变了治疗方案。无进展生存期（39.7±5.1 与 14.2±1.3 个月（p=0.037））和总生存期（57.5±10.7 与 27.9±2.5 个月（p=0.044））在研究组（剂量递增组）明显优于对照组。接受肾切除术和 Memorial Sloan Kettering Cancer Center（MSKCC）评分较低的患者预后较好。在剂量递增后，最常见的不良事件是疲劳、高血压、口腔炎和体重减轻超过 10%的恶化或出现。
结论
在转移性肾细胞癌患者中，特别是在出现轻微进展的情况下，基于可耐受的毒性，递增舒尼替尼剂量是安全的，可以改善预后。对于接受适当教育的患者，建议以 12.5mg 为单位递增剂量。
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