Cushen Samantha J, Power Derek G, Murphy Kevin P, McDermott Ray, Griffin Brendan T, Lim Marvin, Daly Louise, MacEneaney Peter, O' Sullivan Kathleen, Prado Carla M, Ryan Aoife M
School of Food & Nutritional Sciences, University College Cork, Cork, Ireland.
Department of Medical Oncology, Mercy & Cork University Hospitals, Cork, Ireland.
Clin Nutr ESPEN. 2016 Jun;13:e39-e45. doi: 10.1016/j.clnesp.2016.04.001. Epub 2016 May 6.
Body composition may influence clinical outcomes of certain chemotherapeutic agents. We examined the prognostic significance of skeletal muscle mass and adipose tissue on docetaxel toxicity and overall survival in patients with metastatic castrate resistant prostate cancer (mCRPC).
A retrospective review of patients medical records with mCRPC, treated with docetaxel was conducted. Body composition parameters (skeletal muscle mass, muscle attenuation [MA], visceral and subcutaneous adipose tissue) were measured at L3 by computed tomography (CT) and defined using previously established cut points. Toxicity profile was assessed after 3 cycles of the drug and graded according to the National Cancer Institute Common Toxicity Criteria (version 4). Overall survival was analysed.
Overall 63 patients, mean age 69 years (SD 8.3), were included. Sarcopenia was present in 47% (n = 30) and of these 26.7% (8/30) were sarcopenic obese. Common toxicities (all grades) observed included fatigue (80.9%), pain (46%), and constipation (34.9%). DLT occurred in 22 (34.9%) patients; of these 10 patients (15.8%) experienced dose reductions and 12 patients (19%) experienced dose terminations. Measurements of adiposity were not predictive of DLT, however 59.1% patients who had a combination of both sarcopenia and low MA experienced DLT compared to 29.3% of patients without sarcopenia and low MA (p = 0.021). Skeletal muscle index and MA were significantly lower in patients who experienced neutropenia (grade I-II) (46.5 cm/m vs. 51.2 cm/m, p = 0.005) compared to their counterparts (24.6 HU vs. 32.2 HU, p = 0.044). Neither sarcopenia nor sarcopenic obesity was associated with overall survival. In multivariate analysis, BMI ≥25 kg/m (HR: 0.349, CI: 0.156-0.782, p = 0.010) was a significant predictor of longer overall survival and both visceral fat index ≥ median 58.7 cm/m (HR: 2.266 CI: 1.066-4.814, p = 0.033) and anaemia (HR: 2.81, CI: 1.297-6.091, p = 0.009) were significant predictors of shorter overall survival.
Sarcopenia and low MA are associated with neutropenia (grade I-II). Furthermore, presence of anaemia, high volume of visceral fat and BMI <25 kg/m are associated with reduced survival in patients with castrate resistant prostate cancer being treated with docetaxel chemotherapy.
身体组成可能会影响某些化疗药物的临床疗效。我们研究了骨骼肌质量和脂肪组织对转移性去势抵抗性前列腺癌(mCRPC)患者多西他赛毒性和总生存期的预后意义。
对接受多西他赛治疗的mCRPC患者的病历进行回顾性分析。通过计算机断层扫描(CT)在L3水平测量身体组成参数(骨骼肌质量、肌肉衰减[MA]、内脏和皮下脂肪组织),并使用先前确定的切点进行定义。在3个周期的药物治疗后评估毒性特征,并根据美国国立癌症研究所通用毒性标准(第4版)进行分级。分析总生存期。
共纳入63例患者,平均年龄69岁(标准差8.3)。47%(n = 30)的患者存在肌肉减少症,其中26.7%(8/30)为肌肉减少性肥胖。观察到的常见毒性(所有级别)包括疲劳(80.9%)、疼痛(46%)和便秘(34.9%)。22例(34.9%)患者发生剂量限制性毒性(DLT);其中10例患者(15.8%)经历了剂量减少,12例患者(19%)经历了剂量终止。肥胖测量值不能预测DLT,然而,同时存在肌肉减少症和低MA的患者中59.1%发生了DLT,而无肌肉减少症和低MA的患者中这一比例为29.3%(p = 0.021)。发生中性粒细胞减少(I-II级)的患者的骨骼肌指数和MA显著低于未发生者(46.5 cm/m vs. 51.2 cm/m,p = 0.005)(24.6 HU vs. 32.2 HU,p = 0.044)。肌肉减少症和肌肉减少性肥胖均与总生存期无关。在多变量分析中,BMI≥25 kg/m²(风险比:0.349,置信区间:0.156 - 0.782,p = 0.010)是总生存期延长的显著预测因素,而内脏脂肪指数≥中位数58.7 cm/m²(风险比:2.266,置信区间:1.066 - 4.814,p = 0.033)和贫血(风险比:2.81,置信区间:1.297 - 6.091,p = 0.009)均是总生存期缩短的显著预测因素。
肌肉减少症和低MA与中性粒细胞减少(I-II级)相关。此外,贫血、高内脏脂肪量和BMI < 25 kg/m²与接受多西他赛化疗的去势抵抗性前列腺癌患者的生存期缩短相关。