Abstract

Abstract Introduction Radiotherapy remains a mainstay treatment for many cancers often prior to surgery. Radiosensitisers are chemical or pharmaceutical agents that can enhance the effect of radiotherapy on tumour cells and can potentially de-escalate treatments including the need for surgery. Chloroquine (CQ) and Hydroxychloroquine (HCQ) are used as anti-inflammatory and anti-malarial agents but have shown to be promising radio sensitising agents. This systematic review assesses their role as radiosensitisers for the treatment of cancer and explored both pre-clinical and clinical trial evidence. Methods Studies that reported the use of CQ or HCQ as a radiosensitiser as either neoadjuvant or adjuvant therapy were identified via systematic review. It was conducted in accordance with PRISMA guidelines (PROSPERO: CRD42022329779). Five databases were searched for articles. Results 30 papers were selected for review following our screening process. In 6 of the 8 clinical studies, CQ showed disease regression or increased overall survival for patients who were treated with a combination of radiotherapy and CQ. One study did not show any improvement in patient outcomes for HCQ. Most studies were performed for glioblastoma multiforme. 2 of the 3 in vitro/in vivo studies illustrated CQ as a viable radiosensitiser showing reduced tumour growth. However, multiple clinical trials were terminated due to poor patient accrual. Conclusion There are a limited number of preclinical and clinical trials investigating CQ and HCQ as radiosensitisers. There is evidence to suggest CQ may have a role as a radiosensitiser but there needs to be a call for more preclinical and clinical evidence.

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