P01.072  Hydroxychloroquine and short course radiotherapy for elderly patients with glioma: a randomised study

Brazil, Lucy; Swampillai, Angela; Mak, K; Hackshaw, Allan; Edwards, David I.; Mesiri, Pavlina; Clifton‐Hadley, Laura; Shaffer, Richard; Lewis, Joanne; Watts, Colin; Gkogkou, Pinelopi; Chalmers, Anthony J.; Fersht, Naomi; Short, Susan C

doi:10.1093/neuonc/noy139.114

Cited by 3 publications

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“…The included subjects were from 18 countries with a mean or median age of 29 to 78 years old. Four studies [ 26 , 60 , 61 , 63 ] were carried out in COVID-19 patients, whereas the remaining 49 [ 27 – 59 , 62 , 64 – 78 ] were focused on other diseases. HCQ was administered in seven of the eligible studies [ 33 , 63 , 75 – 77 ] for disease prophylaxis, and the remaining studies reported administration for therapeutic use.…”

Section: Resultsmentioning

confidence: 99%

“…HCQ was administered in seven of the eligible studies [ 33 , 63 , 75 – 77 ] for disease prophylaxis, and the remaining studies reported administration for therapeutic use. Thirty-eight of the eligible studies were placebo-controlled, while 15 studies [ 26 , 34 , 36 , 41 , 60 – 62 , 64 , 66 , 68 , 70 , 75 ] stated that no intervention was given to participants in the control group. The daily dosages of HCQ used in ten studies [ 34 , 36 , 37 , 45 , 47 , 61 , 63 , 69 , 75 , 76 ] exceeded 400 mg, and the maximum dosage was 1200 mg once daily [ 36 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…Two studies [ 26 , 61 ] conducted in COVID-19 patients and 30 studies [ 27 – 30 , 32 , 34 , 36 , 37 , 39 , 40 , 42 , 43 , 45 , 47 , 49 , 50 , 53 , 54 , 57 – 59 , 62 , 64 – 66 , 69 , 70 , 75 , 77 , 78 ] in other diseases reported gastrointestinal AEs. The incidence of gastrointestinal AEs in the HCQ group was significantly higher than that in the control group (RD 0.03, 95%CI, 0.01 to 0.06, P = 0.02, I 2 = 55%).…”

Section: Resultsmentioning

confidence: 99%

“…Three studies [ 60 , 61 , 63 ] in COVID-19 patients and 25 studies [ 29 , 32 , 33 , 35 , 37 – 40 , 43 – 46 , 49 , 54 , 56 , 58 , 59 , 64 , 66 , 70 , 75 , 77 ] in patients with other diseases reported skin and subcutaneous tissue AEs. Similarly, the risk of skin and subcutaneous tissue AEs in the HCQ group was significantly different from that in the control group (RD 0.02, 95%CI, 0.00 to 0.03, P = 0.02, I 2 = 25%).…”

Section: Resultsmentioning

confidence: 99%

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Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Chen

Pan

et al. 2020

Eur J Clin Pharmacol

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Introduction Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). Objectives The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. Methods Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. Results We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). Conclusions HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies. Electronic supplementary material The online version of this article (10.1007/s00228-020-02962-5) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Chen

Pan

et al. 2020

Eur J Clin Pharmacol

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“…Higher doses of HCQ are required to adequately inhibit radiation-induced autophagy in patients; however, this may lead to unwanted toxicities (22,134). Subsequent phase I/II clinical trials were also initiated in 2013 by Susan Short's group (Brazil et al; University of Leeds, Leeds, UK) in which the combinatorial effects of lower doses of HCQ and shortcourse radiotherapy were examined in aged patients with high-grade glioma (HGG) (135). HCQ in combination with radiation did not improve patient outcome compared to radiation alone, and in fact, even at the lower doses of HCQ, grade 3-5 toxicities occurred more frequently in patients who received combination treatment compared to radiation alone.…”

Section: Autophagy Inhibition In Clinical Trials Of Radiation Responsementioning

confidence: 99%

The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation

Patel¹,

Sohal

Manjili³

et al. 2020

Radiation Research

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Narrative review of palliative hypofractionated radiotherapy for high grade glioma

Saeed¹,

Tseng²

2021

Ann Palliat Med

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High grade gliomas (HGG) include World Health Organization (WHO) grade III anaplastic astrocytoma (AA) and WHO grade IV glioblastoma (GBM). As genomic alterations are prognostic, even WHO grade II, IDH-wildtype gliomas may be considered as HGG. Current management of HGG include best supportive care (BSC), surgery, radiation therapy (RT), chemotherapy, and a combination. Elderly patients (defined here as age ≥65) with GBM have significantly worse survival compared to younger patients.Similarly, patients with poor performance status [defined as Karnofsky performance status (KPS) <60 or ECOG performance status (PS) >2], regardless of age have worse outcomes. The standard of care for treatment of HGG involves surgery and chemoradiation. However, the optimal treatment in terms of efficacy, safety and maintaining quality of life (QoL), remains a matter of debate in the elderly and/or poor performing patients due to their worse prognosis. Less aggressive interventions are usually reserved for these patients despite surgery providing a survival and neurologic benefit. Improved survival has been noted in elderly patients treated with RT in comparison with those receiving best supportive care (BSC) alone, with similar survival for patients undergoing standard RT (60 Gy/30 fractions) and hypofractionated RT (25-40 Gy in 5-15 daily fractions). An alkylating agent, temozolomide (TMZ), represents a safe and effective option in select patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene. A recent phase III randomized trial for GBM patients (age ≥65 years, ECOG PS 0-2) demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) with hypofractionated RT (40 Gy/15 fractions) with concurrent and adjuvant TMZ vs. RT alone, without adversely impacting either QoL or functional status. Despite chemoradiation becoming the recommended treatment in GBM patients who are elderly but fit, several questions remain unanswered. This includes the survival impact of chemoradiation in patients with severe comorbidities or with ECOG PS >2 or a combination of poor prognostic features such as male gender, poor neurocognition, biopsy only and lack of MGMT methylation.Personalized management of patients with HGG is warranted in the modern era as we attempt to balance the benefit of efficacious treatment with potential toxicity while appreciating the many nuances associated with multiple prognostic factors on anticipated survival. Here, we aim to review the palliative management options available for HGG patients with an emphasis on the role of RT.

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P01.072 Hydroxychloroquine and short course radiotherapy for elderly patients with glioma: a randomised study

Cited by 3 publications

References 0 publications

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation

Narrative review of palliative hypofractionated radiotherapy for high grade glioma

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