Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.
Eur J Cancer. 2012 May;48(7):1031-7. doi: 10.1016/j.ejca.2012.02.050. Epub 2012 Mar 10.
Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib.
We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model.
Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p<0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p<0.0001).
Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.
双膦酸盐被用于预防骨骼转移的骨骼事件，并可能表现出抗肿瘤作用。我们旨在评估双膦酸盐是否可以为接受舒尼替尼治疗的肾细胞癌（RCC）骨转移患者带来缓解率（RR）、无进展生存期（PFS）和总生存期（OS）的获益。
我们对接受舒尼替尼治疗的 RCC 骨转移患者进行了一项多中心回顾性研究。使用卡方检验从列联表和 Cox 回归模型的偏似然检验，对双膦酸盐对 RR、PFS 和 OS 的影响进行了调整，以考虑已知的预后因素。
2004 年至 2011 年间，209 名转移性 RCC 患者接受了舒尼替尼治疗，其中 76 名患者有骨转移，35 名使用双膦酸盐，41 名未使用者。双膦酸盐使用者和未使用者在已知的预后因素方面是平衡的。客观缓解率分别为部分缓解/稳定疾病 86%（n = 30）和 71%（n = 29），进展性疾病 14%（n = 5）和 29%（n = 12）（p = 0.125，OR 2.48）。双膦酸盐使用者的中位 PFS 为 15 个月，而非使用者为 5 个月（HR = 0.55，p<0.0001），中位 OS 未达到（中位随访时间为 45 个月），而非使用者为 14 个月（HR = 0.4，p = 0.029）。在整个患者队列（n = 76）的多变量分析中，与 PFS 相关的因素是双膦酸盐的使用（HR = 0.58，p = 0.035），以及治疗前中性粒细胞与淋巴细胞比值>3（HR = 3.5，p = 0.009）。与 OS 相关的因素是双膦酸盐的使用（HR = 0.5，p = 0.008），碱性磷酸酶升高（HR = 2.9，p = 0.003）和舒尼替尼引起的高血压（HR = 0.63，p<0.0001）。
双膦酸盐可能改善接受舒尼替尼治疗的 RCC 骨转移患者的 RR、PFS 和 OS。
