Yennurajalingam Sriram, Valero Vicente, Lu Zhanni, Liu Diane D, Busaidy Naifa L, Reuben James M, Diaz Fleming Carolina, Williams Janet L, Hess Kenneth R, Basen-Engquist Karen, Bruera Eduardo
1Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine.
2Department of Breast Medical Oncology.
J Natl Compr Canc Netw. 2021 Dec 29;20(3):235-243. doi: 10.6004/jnccn.2021.7066.
Despite the high frequency of cancer-related fatigue (CRF) and its debilitating effects on the quality of life of patients with advanced cancer, there are limited treatment options available. Treatments including physical activity (PA) or dexamethasone (Dex) improve CRF; however, they have lower adherence rates (PA) or long-term adverse effects (Dex). The aim of this study was to determine the feasibility of and preliminary results for the combination of PA and Dex in improving CRF.
In this phase II randomized controlled trial, patients with advanced cancer and CRF scores of ≥4/10 on the Edmonton Symptom Assessment Scale were eligible. Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (LoDex arm) or 8 mg of Dex (HiDex arm) twice a day for 7 days. Feasibility and change in the Functional Assessment of Cancer Illness Therapy-Fatigue subscale (FACIT-F) from baseline to day 8 and day 29 (primary outcome) were assessed. Secondary outcomes included changes in fatigue dimensions (FACIT-General, Patient-Reported Outcomes Measurement Information System [PROMIS]-Fatigue).
A total of 60 of 67 (90%) patients were evaluable. All patients were adherent to study medication. We found that 84% and 65% of patients in the LoDex arm and 96% and 68% of patients in the HiDex arm were adherent to aerobic and resistance exercise, respectively. The FACIT-F effect size in the LoDex arm was 0.90 (P<.001) and 0.92 (P<.001) and the effect size in the HiDex arm was 0.86 and 1.03 (P<.001 for both) at days 8 and 29, respectively. We found significant improvements in the Functional Assessment of Cancer Therapy-Physical (P≤.013) and the PROMIS-Fatigue (P≤.003) at days 8 and 29 in both arms. Mixed-model analysis showed a significant improvement in the FACIT-F scores at day 8 (P<.001), day 15 (P<.001), and day 29 (P=.002). Changes in the FACIT-F scores were not significantly different between patients in the 2 arms (P=.86).
Our study found that the combination therapy of PA with Dex was feasible and resulted in the improvement of CRF. The improvement was seen for up to 3 weeks after the discontinuation of Dex. Further larger studies are justified.
gov identifier: NCT02491632.
尽管癌症相关疲劳（CRF）发生率很高，且对晚期癌症患者的生活质量有严重影响，但可用的治疗选择有限。包括体育活动（PA）或地塞米松（Dex）在内的治疗可改善CRF；然而，它们的依从率较低（PA）或有长期不良反应（Dex）。本研究的目的是确定PA与Dex联合使用改善CRF的可行性及初步结果。
在这项II期随机对照试验中，符合条件的患者为患有晚期癌症且埃德蒙顿症状评估量表上CRF评分≥4/10者。患者被随机分为接受4周标准化PA，同时每天两次服用4毫克Dex（低剂量Dex组）或8毫克Dex（高剂量Dex组），共7天。评估了从基线到第8天和第29天癌症治疗功能评估-疲劳子量表（FACIT-F）的可行性及变化（主要结局）。次要结局包括疲劳维度的变化（FACIT-一般、患者报告结局测量信息系统[PROMIS]-疲劳）。
67例患者中有60例（90%）可评估。所有患者均坚持使用研究药物。我们发现，低剂量Dex组分别有84%和65%的患者坚持有氧运动和抗阻运动，高剂量Dex组分别有96%和68%的患者坚持有氧运动和抗阻运动。在第8天和第29天，低剂量Dex组的FACIT-F效应量分别为0.90（P<0.001）和0.92（P<0.001），高剂量Dex组的效应量分别为0.86和1.03（两者P均<0.001）。我们发现，在第8天和第29天，两组患者的癌症治疗功能评估-身体（P≤0.013）和PROMIS-疲劳（P≤0.003）均有显著改善。混合模型分析显示，在第8天（P<0.001）、第15天（P<0.001）和第29天（P=0.002），FACIT-F评分有显著改善。两组患者FACIT-F评分的变化无显著差异（P=0.86）。
我们的研究发现，PA与Dex联合治疗可行，并可改善CRF。Dex停药后长达3周仍可见改善效果。有必要进行进一步的大型研究。
美国国立医学图书馆临床试验注册中心标识符：NCT02491632。
