Dyspnea is one of the most common and distressing symptoms associated with cancer, occurring in nearly 70% of patients with advanced cancer and intrathoracic malignancies. Dyspnea is associated with impaired function, decreased quality of life, and shortened survival. Current therapies for dyspnea, such as supplemental oxygen and opioids, provide limited relief. Although dyspnea is more difficult to treat than pain is, few clinical trials of therapies for dyspnea have been conducted, and such trials are urgently needed to improve quality of life in cancer patients suffering from this condition. The long-term goal of our research is to develop evidence-based palliative therapies for dyspnea in patients with cancer. Corticosteroids may potentially improve the sensation of dyspnea by modulating the inflammatory response centrally and peripherally and decreasing swelling. On the basis of our preliminary data from a recent clinical trial, we hypothesize that high-dose dexamethasone is effective in treating cancer-related dyspnea. The overall objective of the proposed two-arm, double-blind, parallel (2:1), randomized, controlled trial is to compare the effect of dexamethasone with that of placebo on cancer-related dyspnea. The primary specific aim of this study is to compare the intensity of dyspnea in the dexamethasone arm with that in the placebo arm at week 1. In the second specific aim, we will compare the effects of dexamethasone with those of placebo in terms of personalized dyspnea response (based on a personalized dyspnea goal), unpleasantness of dyspnea, other symptoms, health-related quality of life, respiratory physiologic function, and adverse effects at week 1 and week 2, as well as the intensity of dyspnea at week 2.
The third aim i s to identify predictive markers of dyspnea response to dexamethasone. After obtaining surrogate consent, we will randomize patients to receive either dexamethasone or placebo twice daily for 2 weeks and monitor the patients closely. The proposed study is innovative in that it will cover a novel set of indications (i.e., both intensity and unpleasantness of dyspnea), patient population (i.e., patients with cancer), predictive makers (i.e., inflammatory biomarkers, respiratory physiologic function), and patient-reported outcome measures (i.e., personalized dyspnea response, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events instrument) for dexamethasone. The expected outcome of the proposed study is to establish dexamethasone as a treatment for dyspnea in patients with cancer. These results are expected to have an important positive clinical effect because the effective management of dyspnea will help improve patients' quality of life. This study will also increase our fundamental understanding of the pathophysiology of dyspnea, such as how dexamethasone improves inflammation and respiratory physiologic parameters, which may allow us to devise new and more effective, personalized treatments for this distressing symptom, ultimately moving the field of dyspnea research forward and shifting the treatment paradigm.
The proposed research is relevant to public health because it evaluates a novel therapeutic option? corticosteroids?for cancer-related dyspnea, one of the most common and distressing symptoms in cancer patients. Corticosteroids are not currently routinely used to treat dyspnea, despite strong theoretical and empirical support, and available treatments for dyspnea are lacking. This project is relevant to the NIH's mission because effective management of dyspnea may ultimately help improve function and quality of life for cancer patients suffering from this devastating symptom, and a better understanding of how corticosteroids affect dyspnea will help us to devise newer, more effective treatments for this debilitating condition.
| Hui, David (2018) Benzodiazepines for agitation in patients with delirium: selecting the right patient, right time, and right indication. Curr Opin Support Palliat Care 12:489-494 |
| Hui, David; Hannon, Breffni L; Zimmermann, Camilla et al. (2018) Improving patient and caregiver outcomes in oncology: Team-based, timely, and targeted palliative care. CA Cancer J Clin 68:356-376 |
| Perez-Cruz, Pedro E; Shamieh, Omar; Paiva, Carlos Eduardo et al. (2018) Factors Associated With Attrition in a Multicenter Longitudinal Observational Study of Patients With Advanced Cancer. J Pain Symptom Manage 55:938-945 |
| Hui, David; Hess, Kenneth; Dibaj, Seyedeh S et al. (2018) The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium. Cancer 124:2246-2252 |
| Arthur, Joseph; Hui, David (2018) Safe Opioid Use: Management of Opioid-Related Adverse Effects and Aberrant Behaviors. Hematol Oncol Clin North Am 32:387-403 |
