Etoposide treatment adjunctive to immunosuppressants for critically ill COVID-19 patients

Montero-Baladia, Miguel; Buzón, L; Astigarraga, Itziar; Delgado, Paula Ramos; Iglesias, Emilio; Callejo, Francisco Javier García; López-Veloso, María; Minguito, J; Fernández-Regueras, M; M, Ubeira; Hermida, Gerardo

doi:10.1016/j.jinf.2020.06.006

Cited by 11 publications

(2 citation statements)

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“…In conclusion, in this preliminary experience, combination treatment with etoposide and low-dose corticosteroids resulted in an overall favorable outcome in patients with SARS-CoV-2 infection-associated ARDS. Recently, etoposide has been described as an effective treatment for severe COVID-19 patients who do not require MV ( 12 , 25 ). We plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and low-dose corticosteroids in critically ill COVID-19 patients who are on invasive MV in Japan (jRCT2021210012).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, successful treatment with a combination of etoposide and corticosteroid has been reported in severe ARDS caused by H1N1/09 influenza virus ( 11 ). Recently, in a study of 11 patients with COVID-19 without invasive MV treated with etoposide as salvage therapy ( 12 ), all patients received methylprednisolone plus Tocilizmab (IL-6 inhibitor) or Ankinra (IL-1 inhibitor) before treatment with etoposide. Herein, we report the disease course of five critically ill COVID-19 patients on invasive MV who were treated with a combination of etoposide and corticosteroids.…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids

et al. 2021

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Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) because of limited effective therapies. During infection, the accumulation and activation of macrophages and monocytes in the lungs induce inflammatory mediators and contribute to tissue injury, leading to ARDS. However, therapeutic strategies that directly target activated macrophage and monocytes have not been reported. Combination treatment with etoposide (a cytotoxic agent) and a corticosteroid has been widely used for treating hemophagocytic lymphohistiocytosis characterized by the systemic activation of macrophages with overwhelming inflammation. Herein, we present five cases of COVID-19-associated ARDS treated with etoposide and corticosteroids. Three of the five patients were over 65 years of age and had various underlying diseases, including multiple myeloma. Four patients required invasive mechanical ventilation (MV), and one patient refused to be placed on MV due to underlying diseases. All patients were pre-treated with antiviral and/or other anti-inflammatory agents, but their condition deteriorated and hyperinflammation was noted. All five patients responded well to treatment and had an immediate response, as reflected by improvement in their respiratory condition and inflammatory marker levels and rapid resolution of fever after etoposide administration; however, some patients required a second dose of etoposide and longer course of steroids. All patients recovered, and there were no severe adverse events related to the drugs. Following successful treatment in these five patients, we plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and corticosteroid for treating COVID-19 patients in Japan.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids

et al. 2021

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Etoposide Therapy of Cytokine Storm Syndromes

Henter,

von Bahr Greenwood

2024

Advances in Experimental Medicine and Biology

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Etoposide

2020

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Leucopenia and enterococcal infection following off-label use: case report In a study of 11 patients diagnosed with COVID-19, a 60-year-old woman was described, who developed enterococcus infection and leucopenia following off-label treatment with etoposide for COVID-19. The woman (patient #5 from the article), was admitted following diagnosis of COVID-19 with acute respiratory distress syndrome (ARDS). She was thus put on oxygen support. Her medical history was significant for obesity and hypertension. Initially, she received off-label treatment with lopinavir/ritonavir, methylprednisolone, unspecified antimicrobials and an unspecified interleukin inhibitor. She also received enoxaparin for prophylaxis of thromboembolism. Thereafter, off-label adjuvant salvage treatment with etoposide 100 mg/m 2 [route not stated] was initiated for the COVID-19. She was later transferred to the ICU and required mechanical ventilation. She received a total of two doses of etoposide. The severe ARDS resolved subsequently; however, she developed leucopenia and enterococcus infection, which were considered as etoposide toxicity [durations of treatments to reactions onsets not stated]. She was then shifted out of the ICU. On day 24, she died presumably due to a massive pulmonary thromboembolism [aetiology not stated]. Autopsy was not performed [outcomes of the reactions not stated].

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Etoposide treatment adjunctive to immunosuppressants for critically ill COVID-19 patients

Cited by 11 publications

References 9 publications

Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids

Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids

Etoposide Therapy of Cytokine Storm Syndromes

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