Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Clin Transl Oncol. 2010 Aug;12(8):562-7. doi: 10.1007/s12094-010-0554-0.
For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC.
This study was designed as a retrospective chart review of RCC patients who were treated with CKs and/or TKIs in our department between July 1996 and June 2008. Efficacy and toxicity were assessed using World Health Organization (WHO) criteria. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall (OS) survival.
Ninety-four patients were classified into three groups depending on the modality of treatment administered: 46 were treated with CKs alone and/or chemotherapy (27 with immunotherapy, one with chemotherapy and 18 with both), 28 with TKIs alone (25 with sunitinib and 13 with sorafenib) and 20 with TKIs in second-line treatment following failure with CKs (17 with sunitinib, eight with sorafenib, four with bevacizumab and one with lapatinib). The median age was 60 years in the CK group and 65 and 62, respectively, in TKI in first and second-line treatment groups. Eighty-five percent of patients treated with CKs and 75% in the TKI group in first-line treatment and 80% in second-line treatment were men. Overall, 89% of patients had favourable risk, and 11% had intermediate risk. All patients were considered evaluable for toxicity. The main grade 3-4 (%) toxicity was asthenia for both groups, (ten in TKIs and 15 in CKs). Other grade 1-2 toxicities were mucositis (39), bleeding (8), hypertension (19), skin toxicity (33) and hypothyroidism (12.5) associated with TKIs; and anaemia (33), cough (29), asthenia (39) and emesis (14) associated with CKs. The objective response rate among 80 patients evaluable for activity was 10.6% with CKs and 46.5% and 35%, respectively, with TKIs in first- and second-line treatments. Disease stabilisation with CKs was recorded at 59% of patients and with TKIs 25% and 50% in first- and second-line treatment groups, respectively. The median progression-free survival (PFS) with CKs was 122 days [95% confidence interval (CI) 82-162] and with TKIs 201 days (65-337) in the first and 346 days (256-436) in second-line treatment groups. The median overall survival (OS) was 229 days (142-316) and 2,074 days (1,152-2,996) for patients treated with CKs and TKIs.
Our results are in line with the activity and survival rates previously reported in the literature regarding the use of TKIs for patients with advanced RCC in first- and second-line treatment, which has demonstrated an acceptable toxicity level.
近二十年来，细胞因子（CKs）一直是治疗晚期肾细胞癌（RCC）的唯一全身性治疗选择。近年来，酪氨酸激酶抑制剂（TKIs）已在该肿瘤的治疗中显示出临床活性。我们的目的是描述一个中心使用 CKs 和 TKI 治疗晚期 RCC 患者的经验。
本研究设计为对 1996 年 7 月至 2008 年 6 月期间在我们部门接受 CKs 和/或 TKI 治疗的 RCC 患者的回顾性图表审查。使用世界卫生组织（WHO）标准评估疗效和毒性。使用 Kaplan-Meier 方法估计无进展（PFS）和总（OS）生存。
94 名患者根据治疗方式分为三组：46 名接受 CKs 单独治疗和/或化疗（27 名接受免疫治疗，1 名接受化疗，18 名接受两者），28 名接受 TKI 单独治疗（25 名接受舒尼替尼，13 名接受索拉非尼）和 20 名在 CK 治疗失败后接受 TKI 二线治疗（17 名接受舒尼替尼，8 名接受索拉非尼，4 名接受贝伐珠单抗，1 名接受拉帕替尼）。CK 组的中位年龄为 60 岁，TKI 一线和二线治疗组的中位年龄分别为 65 和 62 岁。接受 CK 治疗的 85%和 TKI 一线治疗的 75%以及二线治疗的 80%的患者为男性。总体而言，89%的患者为低危，11%为中危。所有患者均被认为可评估毒性。主要的 3-4 级（%）毒性是两组的乏力（TKI 组 10 例，CK 组 15 例）。其他 1-2 级毒性包括粘膜炎（39 例）、出血（8 例）、高血压（19 例）、皮肤毒性（33 例）和甲状腺功能减退（12.5%）与 TKI 相关；贫血（33 例）、咳嗽（29 例）、乏力（39 例）和呕吐（14 例）与 CKs 相关。80 名可评估疗效的患者中，CKs 的客观缓解率为 10.6%，TKI 一线和二线治疗的缓解率分别为 46.5%和 35%。CKs 组的疾病稳定率为 59%，TKI 一线和二线治疗组的疾病稳定率分别为 25%和 50%。CKs 的中位无进展生存期（PFS）为 122 天[95%置信区间（CI）82-162]，TKI 一线和二线治疗组分别为 201 天（65-337）和 346 天（256-436）。接受 CKs 和 TKI 治疗的患者的中位总生存期（OS）分别为 229 天（142-316）和 2074 天（1152-2996）。
我们的结果与文献中关于 TKI 在晚期 RCC 一线和二线治疗中的活性和生存率的报道一致，其毒性水平可接受。
