Pharmacologic Interventions for Fatigue in Cancer and Transplantation: A Meta-Analysis

Purpose: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. Results: The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. Recommendations: ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.

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Section: Resultsmentioning

confidence: 99%

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update

et al. 2019

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“…This result is encouraging after long frustration regarding fatigue reduction in oncology care with limited available pharmaceutical options. [28][29][30] Furthermore, this study also demonstrated benefit from minocycline in the cluster of the most severe symptoms, including pain, poor appetite, and shortness of breath, all with a medium ES.…”

Section: Discussionmentioning

confidence: 62%

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

Wang

Shi

Mendoza

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Using a low toxic agent that potentially with anti-inflammatory proprieties, minocycline, we conducted Phase II randomized placebo controlled trial and observed positive effect of reducing fatigue and other symptoms in patients undergoing CRT for NSCLC.Purpose: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, doubleblinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. Methods and Materials: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (AE2 days) area under the curve for symptom burden, which was compared between treatment groups. Results: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 þ adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve Z 31.2 AE 14.2 vs 45.0 AE 20.9, P Z .011), with a large effect size (Cohen's d Z 0.77). Pain (Cohen's d Z 0.54) and shortness of breath (Cohen's d Z 0.55) were also significantly reduced in the minocycline group (all P < .05).

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“…6,26 Three meta-analyses 15,20,22 addressed the addition of iron to an ESA. The remaining 12 meta-analyses 1,2,13,14,[16][17][18][19]21,[23][24][25] addressed ESA versus control (placebo or best standard therapy). The quality of the meta-analyses varied based on AMSTAR2 criteria, such as assessment and discussion of bias and heterogeneity.…”

Section: Resultsmentioning

confidence: 99%

“…Aapro et al 13 reported an increased risk of death in ESA users (odds ratio, 1.20; 95% confidence interval [CI], 1.03 to 1.40) based on nine RCTs in patients with breast cancer. Meta-analyses consistently reported statistically significant reductions in fatigue with ESA use, 1,2,14,23 but the effect sizes were small and unlikely to be clinically important. 35 Little information about treatment intent is available from published studies, but one RCT 6 in the updated literature review restricted to patients with metastatic breast cancer and one meta-analysis 1 developed a decision model that incorporated intent of treatment.…”

Section: Recommendation 12mentioning

confidence: 95%

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

Bohlius

Bohlke

Castelli

et al. 2019

JCO

104

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PURPOSE To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines .

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Pharmacologic Interventions for Fatigue in Cancer and Transplantation: A Meta-Analysis

Abstract: Background Our objective was to determine whether, compared with control interventions, pharmacologic

Cited by 57 publications

References 146 publications

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

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