Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial

Arrieta, Óscar; Hernández‐Pedro, Norma; Maldonado, F.; Ramos‐Ramírez, Maritza; Yamamoto-Ramos, Masao; López-Macías, Diego; Lozano, F.; Zatarain-Barrón, Zyanya Lucía; Turcott, J.; Barrios‐Bernal, Pedro; Orozco‐Morales, Mario; Flores‐Estrada, Diana; Cardona, Andrés Felipe; Rolfo, Christian; Cacho-Díaz, Bernardo

doi:10.1016/j.ijrobp.2022.02.010

Cited by 4 publications

(4 citation statements)

References 52 publications

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“…68 Within the EGFRm subpopulation in the trial, a significant improvement in intracranial PFS was observed in nitroglycerin and WBRT compared with WBRT alone (27.7 vs 10.0 months). 68 This finding suggests that future clinical trials testing nitroglycerin might benefit from preselecting patients with EGFRm. While better known as an antimalarial, chloroquine has been evaluated as a radiosensitiser as evidence of its capacity to improve tumour perfusion or induce apoptosis through autophagy inhibition emerges (figure 3).…”

Section: Candidates With Mixed Resultsmentioning

confidence: 92%

“…11 Another phase II trial, however, showed that concurrent whole brain RT (WBRT) and nitroglycerin in patients with brain metastases (BM) from NSCLC resulted in a better intracranial objective response rate compared with WBRT alone. 68 A high proportion of NSCLC patients with BMs have the epidermal growth factor mutation (EGFRm) subtype, which is associated with increased risks of BM. 68 Within the EGFRm subpopulation in the trial, a significant improvement in intracranial PFS was observed in nitroglycerin and WBRT compared with WBRT alone (27.7 vs 10.0 months).…”

Section: Candidates With Mixed Resultsmentioning

confidence: 99%

“…68 A high proportion of NSCLC patients with BMs have the epidermal growth factor mutation (EGFRm) subtype, which is associated with increased risks of BM. 68 Within the EGFRm subpopulation in the trial, a significant improvement in intracranial PFS was observed in nitroglycerin and WBRT compared with WBRT alone (27.7 vs 10.0 months). 68 This finding suggests that future clinical trials testing nitroglycerin might benefit from preselecting patients with EGFRm.…”

Section: Candidates With Mixed Resultsmentioning

confidence: 99%

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Repurposing radiosensitising medicines for radiotherapy: an overview

Low,

Rodriguez-Berriguete,

Higgins

2024

bmjonc

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Repurposing established non-cancer drugs for the treatment of cancer offers potential benefits such as speed of clinical translation and financial efficiencies. In this study, we assess the landscape of repurposing drugs for combined use with radiotherapy (RT) based on their capacity to increase tumour radiosensitivity. Using a literature-based approach, we identified 42 radiosensitising drugs with varied non-cancer indications and mechanisms of action, that have entered or completed clinical trials in combination with RT or with chemoradiotherapy. Two compounds, nicotinamide and nimorazole, have entered routine but limited clinical use in combination with radiotherapy. We provide an overview on these successfully repurposed drugs, and highlight some examples of unsuccessful repurposing efforts and drug candidates with an uncertain prospect of success. Upon reviewing the trials, we identified some common themes behind the unsuccessful efforts, including poor trial reporting, absence of biomarkers and patient selection, sub-optimal pharmacological properties, inappropriate trial design, lack or inadequate consideration of pre-clinical and clinical data, and limited funding support. We point out future directions to mitigate these issues and increase the likelihood of success in repurposing drug treatments for radiotherapy.

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Section: Candidates With Mixed Resultsmentioning

confidence: 92%

Section: Candidates With Mixed Resultsmentioning

confidence: 99%

Section: Candidates With Mixed Resultsmentioning

confidence: 99%

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Repurposing radiosensitising medicines for radiotherapy: an overview

Low,

Rodriguez-Berriguete,

Higgins

2024

bmjonc

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“…In a study randomly including stage-IV NSCLC brain metastasis patients treated with whole brain radiation therapy and nitroglycerine or WBRT alone found increased PFS and ORR in nitroglycerine group compared to placebo. There was no difference in OS in nitroglycerine treatment group compared to placebo [23]. In meta-analysis of randomized controlled studies and observational studies separately conducted on of lung cancer patients treated with statins found increased OS [24, 25].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

Samadder

2023

Preprint

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AimThe aim of this study is to identify literature suggesting drug repurposing based on various medicines found to possess enhanced efficacy against lung cancer in humans based on pre-clinical and retrospective analysis. Often pre-clinical and retrospective study findings may deviate from the results of randomized prospective clinical studies, this study intends to identify the efficacious new drugs against lung cancer in placebo-controlled studies.MethodsA systematic review of literature was performed in PubMed database on 30thAugust 2023 without any fixed timeline with terms related to ‘drug repurposing’ and ‘Lung cancer’. Post screening of literature, the names of non-chemo drugs identified were further searched inclinicaltrials.govadditionally NCT# was searched in google scholar, in-case the trial results were not available in respective source to validate the study findings.ResultsIn PubMed 513 articles were found, 9% articles mentioned about drugs with potential efficacy against lung cancer in humans. In these 45 articles 61 non-chemo drugs were identified from specific 293 clinical studies. Among these 30 studies for 23 drugs were in advanced clinical stage and 9 non-chemo medicines were identified to have positive results in randomized controlled clinical trials, rest of the drugs failed to attend designated clinical efficacy till-date. Anti-alcoholism, anti-bacterial, anti-emetics, cox-2 inhibitors, and HMG-CoA reductase inhibitor are the drugs that could potentially effective against advanced non-small cell lung cancer.ConclusionApplying the advanced search methodology to identify drugs repurposed or approved for targeted disease. All these 9 non-chemo were screened under randomized trial and currently only one drug disulfiram was found to enhance survival and response, reduced disease progression, in advanced NSCLC originally indicated for anti-alcoholism.

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OncoFlash – Research Updates in a Flash! (May edition)

Crockett

Lorimer

2022

Clinical Oncology

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Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial

Cited by 4 publications

References 52 publications

Repurposing radiosensitising medicines for radiotherapy: an overview

Repurposing radiosensitising medicines for radiotherapy: an overview

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

OncoFlash – Research Updates in a Flash! (May edition)

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