Department of Urology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
BJU Int. 2012 Sep;110(6 Pt B):E228-34. doi: 10.1111/j.1464-410X.2011.10905.x. Epub 2012 Feb 14.
What's known on the subject? and What does the study add? Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, sorafenib and sunitinib, have been reported to show little cross-resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients. This case series shows that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment. Outcomes of the sorafenib rechallenge were not significantly affected by the response to the initial sorafenib treatment or by the duration of intervening treatments between first sorafenib and rechallenge.
To investigate clinical outcomes of sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC).
Patients with metastatic RCC who received sorafenib rechallenge after failed treatment first with sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression-free survival (PFS), and adverse events (AEs).
Of the 14 patients who received sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon-α (nine patients) and interleukin-2 (six patients), with a median duration of 9 months. The best responses after the first sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients. Rechallenge with sorafenib was undertaken after a 7.6 month median interval from the initial sorafenib challenge. Eight patients achieved SD on sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8-7.0) months. The outcome of the sorafenib rechallenge was not significantly affected by the response to the initial sorafenib treatment or by the duration of treatments received between first sorafenib and rechallenge. No severe AE was newly observed on the rechallenge.
In the systemic treatment of advanced RCC, it was suggested that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment.
研究索拉非尼序贯治疗转移性肾细胞癌（RCC）患者中索拉非尼再次挑战的临床结果。
回顾性分析了 14 例接受索拉非尼再次挑战的转移性 RCC 患者的患者特征、最佳反应、无进展生存期（PFS）和不良事件（AE）。
12 例患者可评估反应。11 例患者先前接受过肾切除术，10 例患者先前接受过系统治疗，主要为干扰素-α（9 例）和白细胞介素-2（6 例），中位时间为 9 个月。首次索拉非尼治疗的最佳反应分别为 2 例部分缓解（PR）、7 例稳定疾病（SD）和 2 例进展性疾病（PD）。中位 PFS 为 5.7 个月。由于 PD，8 例患者初始索拉非尼治疗停止，4 例患者因 AE 停止。在初始索拉非尼挑战后中位间隔 7.6 个月开始再次使用索拉非尼。8 例患者在索拉非尼再次挑战中达到 SD，中位 PFS 为 5.4（95%置信区间，3.8-7.0）个月。索拉非尼再次挑战的结果不受初始索拉非尼治疗反应或首次索拉非尼与再次挑战之间接受治疗时间的影响。再次挑战时未观察到新的严重 AE。
在晚期 RCC 的系统治疗中，提示对索拉非尼耐药的患者在序贯治疗中再次使用索拉非尼可能会重新控制疾病。
