Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy

Janowitz, Tobias; Kleeman, Sam O.; Vonderheide, Robert H.

doi:10.1002/onco.13680

Cited by 27 publications

(20 citation statements)

References 66 publications

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“…Numerous studies have reported that emodin treatment can significantly decrease the production of serum AMY and inflammatory mediators or cytokines in lung tissues (27,40). Additionally, DEX has been shown to act as a non-specific immune inhibitor (42). It was reported that its use inhibited the production of numerous inflammatory mediators and increased the synthesis of proteins associated with anti-inflammatory responses (43).…”

Section: Discussionmentioning

confidence: 99%

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

Jiang

Luo

et al. 2021

Exp Ther Med

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Severe acute pancreatitis (SAP) activates the systemic inflammatory response and is potentially lethal. The aim of the present study was to determine the effects of emodin on acute lung injury (ALI) in rats with SAP and investigate the role of the Nod-like receptor protein 3 (NLRP3) inflammasome and its association with neutrophil recruitment. Sodium taurocholate (5.0%) was used to establish the SAP model. All animals were randomly assigned into four groups: Sham, SAP, emodin and dexamethasone (positive control drug) groups (n=10 mice per group). Histopathology observation of pancreatic and lung tissues was detected by hematoxylin and eosin staining. The levels of serum amylase, IL-1β and IL-18 were measured by ELISA. Single-cell suspensions were obtained from enzymatically digested lung tissues, followed by flow cytometric analysis for apoptosis. In addition, the expression levels of NLRP3 inflammasome-associated and apoptosis-associated proteins in lung tissues were measured by western blotting. Moreover, lymphocyte antigen 6 complex locus G6D + (Ly6G + ) cell recruitment was detected using immunohistochemical analysis. The results revealed that emodin markedly improved pancreatic histological injury and decreased the levels of serum amylase, IL-1β and IL-18. Pulmonary edema and apoptosis were significantly alleviated by emodin. Additionally, the protein expression levels of intercellular adhesion molecule 1, NLRP3, apoptosis-associated speck-like protein containing a CARD and cleaved caspase-1 were downregulated following emodin treatment. Moreover, emodin inhibited Ly6G + cell recruitment in lung tissues. The present study demonstrated that emodin may offer protection against ALI induced by SAP via inhibiting and suppressing NLRP3 inflammasome-mediated neutrophil recruitment and may be a novel therapeutic strategy for the clinical treatment of ALI.

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Section: Discussionmentioning

confidence: 99%

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

Jiang

Luo

et al. 2021

Exp Ther Med

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“…These antibodies prevent tumor immune tolerance by blocking ligand-receptor interactions and subsequent effector signaling that ultimately inhibit anti-tumor immune responses [50]. The use of ICIs has revolutionized oncology and induced substantial leaps in the treatment of a wide range of tumors including melanoma and non-small cell lung cancer (NSCLC) [51], both capable of metastasis to the brain. Several studies assessing ICI utility in brain tumors were compiled in a large systematic review and demonstrated a moderate response to ICI in melanoma and NSCLC brain metastases with some clinical effects in glioblastoma [51].…”

Section: Icismentioning

confidence: 99%

Steroid utility, immunotherapy, and brain tumor management: an update on conflicting therapies

Goldman¹,

Lucke‐Wold

Martínez-Sosa

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

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Steroid use is a widely accepted practice for both the treatment and prevention of tumor-induced edema, but there are many unknowns regarding their current clinical utility with modern anti-tumor therapies. This decreases edema and relieves the symptomatic mass effect. There are clearly understood benefits and commonly accepted complications of methylprednisolone (MP) use, but the topic is recently controversial. With immunotherapy advancing, a robust immune response is crucial for full therapeutic efficacy. The immunosuppression of MP may interfere with future and current therapeutics relying on the integrity of the patient’s immune system. This further emphasizes the need for alternative agents to effectively treat tumor-induced cerebral edema. This review highlights the current clinical utility of steroids to treat brain tumor-related edema and the underlying pathophysiology. It also reviews details regarding different steroid formulations and dosing. Research available regarding concurrent steroid use with immunotherapy is detailed next, followed by alternatives to steroids and barriers to their adoption. Finally, this paper discusses pre-clinical findings and emerging treatments aimed to augment or replace steroid use.

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“…In cisplatin-based chemotherapy, no clear-cut conclusion can be drawn from studies currently available [ 143 , 144 ]. In patients receiving immunotherapy, the lowest effective dose of dexamethasone is recommended [ 145 ] and the lowest effective dose is also recommended for prophylaxis of CINV during the COVID-19 pandemic [ 146 ]. This is of special interest for older cancer patients, because the single-day dexamethasone strategy enables the entire antiemetic prophylaxis to be administered before chemotherapy with no need for routine antiemetics in the subsequent days, resulting in optimal compliance.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes

2021

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Chemotherapy-induced nausea and vomiting (CINV) are still two of the most feared side effects of cancer therapy. Although major progress in the prophylaxis of CINV has been made during the past 40 years, nausea in particular remains a significant problem. Older patients have a lower risk of CINV than younger patients, but are at a higher risk of severe consequences of dehydration and electrolyte disturbances following emesis. Age-related organ deficiencies, comorbidities, polypharmacy, risk of drug–drug interactions, and lack of compliance all need to be addressed in the older patient with cancer at risk of CINV. Guidelines provide evidence-based recommendations for the prophylaxis of CINV, but none of these guidelines offer specific recommendations for older patients with cancer. This means that the recommendations may lead to overtreatment in some older patients. This review describes the development of antiemetic prophylaxis of CINV focusing on older patients, summarizes recommendations from antiemetic guidelines, describes deficiencies in our knowledge of older patients, summarizes necessary precautions, and suggests some future perspectives for antiemetic research in older patients.

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Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy

Cited by 27 publications

References 66 publications

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

Steroid utility, immunotherapy, and brain tumor management: an update on conflicting therapies

Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes

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