Combination Therapy of Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Phase II Randomized Double-Blind Controlled Trial

Authors:
Sriram Yennurajalingam Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine;

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 MD, MS, FAAHPM
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Vicente Valero Department of Breast Medical Oncology;

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 MD
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Zhanni Lu Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine;

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 DrPH
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Diane D. Liu Department of Biostatistics;

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Naifa L. Busaidy Department of Endocrine Neoplasia and Hormonal Disorders;

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 MD
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James M. Reuben Department of Hematopathology; and

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Carolina Diaz Fleming Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine;

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Janet L. Williams Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine;

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Kenneth R. Hess Department of Biostatistics;

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Karen Basen-Engquist Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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Eduardo Bruera Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine;

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Background: 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. Methods: 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). Results: 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). Conclusions: 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.

ClinicalTrials.gov identifier: NCT02491632.

Submitted March 8, 2021; final revision received June 4, 2021; accepted for publication June 4, 2021. Published online December 29, 2021.

Author contributions: Study concept and design: Yennurajalingam, Bruera. Data acquisition, analysis, or interpretation: Valero, Lu, Liu, Busaidy, Reuben, Diaz Fleming, Williams, Hess, Basen-Engquist. Drafting and critical revision of the manuscript: All authors. Statistical analysis: Yennurajalingam, Lu, Liu, Hess. Administrative, technical, or material support: Yennurajalingam, Bruera. Supervision: Yennurajalingam, Bruera. Full access to all data in the study and responsibility for data integrity and accuracy of data analysis: Yennurajalingam.

Disclosures: Dr. Yennurajalingam has disclosed receiving grant/research support from Helsinn Healthcare and Genentech. Dr. Valero has disclosed serving as a consultant for Amgen, Inc.; Cancer Expert Now, Inc.; and Genomic Health, Inc. Dr. Bruera has disclosed receiving grant/research support from Helsinn Healthcare. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by funding from the University Cancer Foundation (award identification number 002).

Correspondence: Sriram Yennurajalingam, MD, MS, FAAHPM, Department of Palliative Care, Rehabilitation, and Integrative Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1414, Houston, TX 77030. Email: syennu@mdanderson.org

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