Shi Hong-Zhe, Tian Jun, Chen Xi, Wang Dong, Li Chang-Ling
Department of Urology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Urology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Clin Genitourin Cancer. 2017 Feb;15(1):139-144. doi: 10.1016/j.clgc.2016.05.007. Epub 2016 May 27.
Sunitinib is approved multinationally for the first-line treatment of metastatic renal cell carcinoma (mRCC). After mRCC progressed in patients, we escalated the sunitinib dose in selected patients and then retrospectively evaluated the efficacy and safety of dose-escalated sunitinib in these selected patients.
From January 2010 to January 2016, 288 patients with mRCC received sunitinib as first-line treatment. Treatment continued until radiologic progression occurred. When the disease progressed, 34 patients with mRCC who had mild or moderate adverse events and missed free second-line target therapy trials were escalated to sunitinib 50 mg once daily continuously. Dose-escalated treatment continued until the disease progressed again, the patient was unable to tolerate sunitinib, or the patient was willing to quit the sunitinib treatment.
All 34 patients (median age, 55 years [range, 28-67 years]; 28 [82.4%] males; 6 [17.6%] females) with confirmed metastatic clear-cell RCC, received an escalated dose of sunitinib and were evaluated for toxicity and response. During treatment at the regular sunitinib dosage, 9 (26.5%) patients achieved partial response and 25 (73.5%) patients had a stable disease condition. With dose-escalated sunitinib, 2 (5.9%) patients achieved partial response, 27 (79.4%) patients had stable disease, and the disease still progressed in 5 (14.7%) patients. Tumor size was reduced in 10 (38.2%) patients. Median progression-free survival was 11.2 months (95% confidence interval [CI], 5.2-17.2 months) with the regular dose of sunitinib. During dose-escalated sunitinib treatment, the median progression-free survival was 4.1 months (95% CI, 2.3-5.9 months). Median overall survival was 25.0 months from the initiation of sunitinib treatment (95% CI, 16.0-34.0 months). During dose escalation, grade 3 adverse events consisted of hand-foot syndrome, fatigue, mucositis, and diarrhea. All grade 3 adverse events were relieved by supporting and symptomatic treatment. No grade 4 adverse events occurred.
Sunitinib was efficacious in the treatment of mRCC. For patients who tolerated sunitinib well, the dosage could be cautiously increased to gain better treatment benefit.
舒尼替尼已在多国获批用于转移性肾细胞癌（mRCC）的一线治疗。在mRCC患者病情进展后，我们对部分患者增加了舒尼替尼剂量，然后回顾性评估了剂量增加后的舒尼替尼在这些选定患者中的疗效和安全性。
2010年1月至2016年1月，288例mRCC患者接受舒尼替尼一线治疗。治疗持续至出现影像学进展。当疾病进展时，34例发生轻度或中度不良事件且未接受免费二线靶向治疗试验的mRCC患者被升级为每日一次持续服用50 mg舒尼替尼。剂量增加后的治疗持续至疾病再次进展、患者无法耐受舒尼替尼或患者愿意停止舒尼替尼治疗。
所有34例确诊为转移性透明细胞RCC的患者（中位年龄55岁[范围28 - 67岁]；28例[82.4%]为男性；6例[17.6%]为女性）接受了剂量增加的舒尼替尼治疗，并对毒性和反应进行了评估。在常规舒尼替尼剂量治疗期间，9例（26.5%）患者获得部分缓解，25例（73.5%）患者病情稳定。剂量增加后的舒尼替尼治疗中，2例（5.9%）患者获得部分缓解，27例（79.4%）患者病情稳定，5例（14.7%）患者疾病仍进展。10例（38.2%）患者肿瘤大小缩小。常规剂量舒尼替尼治疗的中位无进展生存期为11.2个月（95%置信区间[CI]，5.2 - 17.2个月）。在剂量增加后的舒尼替尼治疗期间，中位无进展生存期为4.1个月（95% CI，2.3 - 5.9个月）。从开始使用舒尼替尼治疗起，中位总生存期为25.0个月（95% CI，16.0 - 34.0个月）。在剂量增加期间，3级不良事件包括手足综合征、疲劳、黏膜炎和腹泻。所有3级不良事件经支持治疗和对症治疗后缓解。未发生4级不良事件。
舒尼替尼对mRCC治疗有效。对于能很好耐受舒尼替尼的患者，可谨慎增加剂量以获得更好的治疗效益。
