Efficacy of Methylprednisolone on Pain, Fatigue, and Appetite Loss in Patients With Advanced Cancer Using Opioids: A Randomized, Placebo-Controlled, Double-Blind Trial

Paulsen, Ørnulf; Klepstad, Pål; Rosland, Jan Henrik; Aass, Nina; Albert, Eva; Fayers, Peter; Kaasa, Stein

doi:10.1200/jco.2013.54.3926

Cited by 170 publications

(126 citation statements)

References 34 publications

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“…Of the three clusters identified by principal component analysis, we found significant improvement in the FAD cluster scores compared with placebo at day 8 and day 15 of treatment. Prior studies on the use of steroids showed short-term beneficial effects on cancer-related fatigue and anorexia [50][51][52]. However, no studies have investigated the use of steroids for the treatment of depression in advanced cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report

et al. 2016

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Objective. Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer. Methods. We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment. Results. A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/ depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment. Conclusion. The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia-cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. The Oncologist 2016; 21:384-390Implications for Practice: Results of this preliminary study suggest that fatigue-anorexia/cachexia/depression cluster scores significantly improved in the dexamethasone treatment group as compared with placebo.These findings indicate that symptoms in the fatigue/anorexia-cachexia/depression cluster might share a common causative mechanism. Further studies are needed to validate these findings.

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Section: Discussionmentioning

confidence: 99%

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report

et al. 2016

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“…All of the 2443 patients who received opioids had poor systemic conditions, as indicated by baseline PPS 35 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). The most common tumor type was respiratory tract tumor.…”

Section: Discussionmentioning

confidence: 99%

“…31) Concomitant use of antipsychotic, hypnotic, or antidepressant drugs may enhance central nervous system depressant effect and affect the respiratory function. Nevertheless, the current study demonstrated that opioid antagonists ameliorated respiratory depression in all cases, implying lesser effect of concomitant drugs on respiratory function.…”

Section: Discussionmentioning

confidence: 99%

A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids

Uekuzu

Higashiguchi

Futamura

et al. 2017

Biological & Pharmaceutical Bulletin

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There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

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“…However, it is unknown whether corticosteroids are effective in treating chemotherapy-related fatigue and/or malaise. During palliative care, the standard daily steroid dose for relieving fatigue is 2–8 mg of betamethasone and DEX, or 15–30 mg of prednisolone [6, 8, 9, 15-17]. Although some patients in this study might have approached the palliative care period, the use of higher doses (4–8 mg/day) of DEX is associated with the substantial possibility of AEs, which might adversely affect quality of life in the context of long-term cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402)

et al. 2018

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Background: Regorafenib is an oral multikinase inhibitor with a proven survival benefit for metastatic colorectal cancer patients. The KSCC1402/HGCSG1402 study investigated the prophylactic effect of oral dexamethasone (DEX) on regorafenib-related fatigue and/or malaise. Patients and Methods: Patients who progressed after standard chemotherapy were randomized 1: 1 to a DEX group (2 mg/day; days 1–28) with regorafenib or a placebo group with regorafenib. The primary endpoint was the incidence of fatigue and/or malaise, based on version 4.0 of the National Cancer Institute’s CTCAE (Common Terminology Criteria for Adverse Events). One of the secondary endpoints was the incidence of fatigue and/or malaise based on the CTCAE assessed by patient-reported outcome (PRO). Results: The incidence of any grade of fatigue and/or malaise assessed by the investigators was 58.8% in the DEX group and 61.1% in the placebo group (p = 0.8101), and that assessed by PRO was 47.2 and 58.3%, respectively (p = 0.3450). The incidence of grade ≥2 fatigue and/or malaise, as assessed by the investigators, was 19.4% for the DEX group and 38.9% for the placebo group (p = 0.0695), and that assessed by PRO was 27.8 and 52.8%, respectively (p = 0.0306). Conclusion: Our results suggest that prophylactic oral DEX is clinically effective in improving regorafenib-related fatigue and/or malaise.

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Efficacy of Methylprednisolone on Pain, Fatigue, and Appetite Loss in Patients With Advanced Cancer Using Opioids: A Randomized, Placebo-Controlled, Double-Blind Trial

Abstract: MP 32 mg daily did not provide additional analgesia in patients with cancer receiving opioids, but it improved fatigue, appetite loss, and patient satisfaction. Clinical benefit beyond a short-term effect must be examined in a future study.

Cited by 170 publications

References 34 publications

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report

A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402)

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