All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
J Clin Oncol. 2017 Jun 1;35(16):1764-1769. doi: 10.1200/JCO.2016.71.1184. Epub 2017 Jan 23.
Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment). Patients with a ≥ 10% reduction in tumor burden (TB) after four cycles had sunitinib held, with restaging scans performed every two cycles. Sunitinib was reinitiated for two cycles in those patients with an increase in TB by ≥ 10%, and again held with ≥ 10% TB reduction. This intermittent sunitinib dosing continued until Response Evaluation Criteria in Solid Tumors-defined disease progression while receiving sunitinib, or unacceptable toxicity occurred. The primary objective was feasibility, defined as the proportion of eligible patients who underwent intermittent therapy. Results Of 37 patients enrolled, 20 were eligible for intermittent therapy and all patients (100%) entered the intermittent phase. Patients were not eligible for intermittent sunitinib because of progressive disease (n = 13), toxicity (n = 1), or consent withdrawal (n = 3) before the end of cycle 4. The objective response rate was 46% after the first four cycles of therapy. The median increase in TB during the periods off sunitinib was 1.6 cm (range, -2.9 to 3.4 cm) compared with the TB immediately before stopping sunitinib. Most patients exhibited a stable sawtooth pattern of TB reduction while receiving sunitinib and TB increase while not receiving sunitinib. Median progression-free survival to date is 22.4 months (95% CI, 5.4 to 37.6 months) and median overall survival is 34.8 months (95% CI, 14.8 months to not applicable). Conclusion Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.
目的 舒尼替尼是转移性肾细胞癌（mRCC）的标准初始治疗药物，但慢性给药需要在毒性和临床获益之间取得平衡。本研究旨在探讨间歇式舒尼替尼给药在 mRCC 患者中的可行性和临床结局。
方法 本研究纳入了未经治疗的、透明细胞 mRCC 患者，给予 4 个周期的舒尼替尼治疗（50mg/天，连续服用 4 周，然后停药 2 周）。4 个周期后肿瘤负荷（TB）至少减少 10%的患者暂停舒尼替尼治疗，每 2 个周期进行一次重新评估。如果 TB 增加≥10%，则再次给予 2 个周期的舒尼替尼治疗，当 TB 再次减少≥10%时则再次停药。只要患者在接受舒尼替尼治疗期间出现 RECIST 定义的疾病进展或不可接受的毒性，就持续进行这种间歇式舒尼替尼给药。主要研究终点为可行性，定义为接受间歇治疗的合格患者比例。
结果 在纳入的 37 例患者中，有 20 例患者符合间歇治疗条件，所有患者（100%）均进入间歇治疗阶段。由于疾病进展（n=13）、毒性（n=1）或在第 4 周期结束前撤回同意（n=3），有 13 例患者在第 4 周期结束前未接受间歇式舒尼替尼治疗。经过 4 个周期的初始治疗后，患者的客观缓解率为 46%。在停止使用舒尼替尼期间，TB 的中位数增加了 1.6cm（范围：-2.9 至 3.4cm），而在停止使用舒尼替尼前，TB 的中位数减少了 1.6cm。大多数患者在接受舒尼替尼治疗时 TB 呈锯齿状下降，而在未接受舒尼替尼治疗时 TB 呈上升趋势。截至目前，中位无进展生存期为 22.4 个月（95%CI：5.4 至 37.6 个月），中位总生存期为 34.8 个月（95%CI：14.8 个月至无法评估）。
结论 周期性延长舒尼替尼治疗间歇期是可行的，且临床疗效似乎并未受到影响。
