Department of Pharmacy Clinical Programs, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
J Urol. 2014 Mar;191(3):611-8. doi: 10.1016/j.juro.2013.08.090. Epub 2013 Sep 7.
We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes.
We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression.
A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p <0.05).
Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.
我们确定了舒尼替尼替代方案，在减少转移性肾细胞癌患者不良反应的同时保持剂量强度。我们还确定了替代方案对临床结果的影响。
我们回顾性分析了 2006 年 1 月 26 日至 2011 年 3 月 1 日期间在我们主要综合癌症中心接受一线舒尼替尼治疗的年龄在 18 岁或以上的透明细胞转移性肾细胞癌患者的记录。一部分患者在首次出现不可耐受的不良反应时，从传统的 28 天治疗 14 天休息方案改为 14 天治疗 7 天休息方案或其他替代方案。对照组接受标准剂量减少。我们使用 Kaplan-Meier 法估计无进展生存期和总生存期。使用 Cox 回归分析无进展生存期和总生存期的预测因素。
共有 187 例患者纳入分析，其中 87%的患者在基线时接受传统方案。在治疗过程中，53%的患者继续接受传统方案，47%的患者开始或转为替代方案。基线特征相似。促使方案改变的不良反应包括乏力（64%）、手足综合征（38%）和腹泻（32%）。改为替代方案的中位时间为 5.6 个月。传统方案的中位总生存期为 17.7 个月（95%CI 10.8-22.2），而替代方案的中位总生存期为 33.0 个月（95%CI 29.3-不可估计）（p<0.0001）。多变量分析显示，东部合作肿瘤学组（ECOG）表现状态较差、乳酸脱氢酶升高、白蛋白降低、亨氏标准不利和传统方案与总生存期缩短相关（p<0.05）。
在转移性肾细胞癌患者中，舒尼替尼替代方案的给药可能会减轻不良反应，同时获得与传统方案相当的结果。需要对替代剂量方案进行前瞻性研究。
