Association of Skeletal Muscle Wasting With Treatment With Sorafenib in Patients With Advanced Renal Cell Carcinoma: Results From a Placebo-Controlled Study
Association of Skeletal Muscle Wasting With Treatment With Sorafenib in Patients With Advanced Renal Cell Carcinoma: Results From a Placebo-Controlled Study
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DOI：
10.1200/jco.2009.24.9730
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发表时间：
2010-02-20
影响因子：
45.3
通讯作者：
Baracos, Vickie E.
中科院分区：
文献类型：
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作者：
Antoun, Sami;Birdsell, Laura;Baracos, Vickie E.
目的特异性抗肿瘤治疗对肿瘤相关消瘦进展的影响尚不明确。我们选择了靶向治疗索拉非尼，因为有报道称它与减肥有关。在一项随机、双盲临床试验中，对标准治疗有耐药性的转移性肾细胞癌（RCC）患者（N = 80）接受索拉非尼400 mg，每日2次或安慰剂治疗。计算机断层扫描图像分析对特定肌肉和脂肪组织的评估具有高精度和特异性，用于确定总骨骼肌和脂肪组织的变化。结果纳入时，51%的患者超重或肥胖（即体重指数[BMI]在25 kg/m(2)以下）。只有5%体重过轻。72%的BMI小于25的患者和34%的BMI大于25的患者出现了严重的肌肉萎缩（即肌肉减少症）。患者平均接受安慰剂治疗6个月，接受索拉非尼治疗1年。安慰剂组患者在6个月内体重稳定（0.8 kg +/- 0.7 kg），肌肉或脂肪无明显变化。接受索拉非尼治疗的患者6个月减重2.1 kg +/- 0.6 kg (P < 0.01)， 1年减重4.2 kg +/- 0.7 kg （P < 0.01）。索拉非尼组患者在6个月（减少4.9%,P < 0.01）和12个月（减少8.0%,P < 0.01）逐渐丧失骨骼肌。结论肌少症在转移性肾细胞癌患者中普遍存在，在BMI正常或高的患者中是一种隐性疾病。索拉非尼特别加重了肌肉损失，这与激酶在调节肌肉质量中的作用的证据一致。肌肉损失是索拉非尼的不良反应，可能与虚弱、疲劳和身体残疾有关。
PurposeEffects of specific antineoplastic therapies on progression of cancer-associated wasting remain uncharacterized. We selected a targeted therapy, sorafenib, because of its reported association with weight loss.Patients and MethodsPatients with metastatic renal cell cancer (RCC) who were resistant to standard therapy (N = 80) received sorafenib 400 mg twice daily or placebo in a randomized, double-blinded clinical trial. Computed tomography image analysis, which has high precision and specificity for evaluation of specific muscles and adipose tissues, was used to define change in total skeletal muscle and adipose tissue.ResultsAt inclusion, 51% of patients were overweight or obese (ie, body mass index [BMI] > 25 kg/m(2)). Only 5% were underweight. Advanced muscle wasting (ie, sarcopenia) was present in 72% of patients with BMI less than 25 and in 34% of those with a BMI greater than 25. Patients received placebo for an average of 6 months and received sorafenib for 1 year. Patients in the placebo group had stable body weight during 6 months (0.8 kg +/- 0.7 kg), with no significant alteration of muscle or fat. Patients who received sorafenib lost 2.1 kg +/- 0.6 kg (P < .01) in 6 months and lost 4.2 kg +/- 0.7 kg (P < .01) by 1 year. Sorafenib-treated patients lost skeletal muscle progressively at 6 months (decrease of 4.9%; P < .01) and 12 months (decrease of 8.0%; P < .01).ConclusionSarcopenia is prevalent in patients with metastatic RCC and is an occult condition in patients with normal or high BMI. Muscle loss is specifically exacerbated by sorafenib, consistent with the evidence for a role of kinases in regulating muscle mass. Muscle loss is a sorafenib adverse effect that may relate to asthenia, fatigue, and physical disability.