ArticleEuropean journal of cancer (Oxford, England : 1990)2019
Buparlisib with thoracic radiotherapy and its effect on tumour hypoxia: A phase I study in patients with advanced non-small cell lung carcinoma.
Article in European journal of cancer (Oxford, England : 1990), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Use and Reporting of Patient-Reported Outcomes in Trials of Palliative Radiotherapy: A Systematic Review.JAMA network open · 2022Pooled it
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- Review
- Early Reduction of Glucose Consumption Is a Biomarker of Kinase Inhibitor Efficacy Which Can Be Reversed with GLUT1 Overexpression in Lung Cancer Cells.Molecular imaging and biology · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Timing of hypoxia PET/CT imaging after 18F-fluoromisonidazole injection in non-small cell lung cancer patients.Scientific reports · 2022Article
- Drivers of Radioresistance in Prostate Cancer.Journal of clinical medicine · 2022Review
- Combining radiation with PI3K isoform-selective inhibitor administration increases radiosensitivity and suppresses tumor growth in non-small cell lung cancer.Journal of radiation research · 2022Article
- Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.Nature reviews. Clinical oncology · 2022Review
- Developing PI3K Inhibitors for Respiratory Diseases.Current topics in microbiology and immunology · 2022Article
- Investigation of atovaquone-induced spatial changes in tumour hypoxia assessed by hypoxia PET/CT in non-small cell lung cancer patients.EJNMMI research · 2021Article
- Targeting PI3K/Akt signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
- Therapeutic targeting of the hypoxic tumour microenvironment.Nature reviews. Clinical oncology · 2021Review
- Review
- Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- HighOncotarget · 2021Article
- Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.Frontiers in oncology · 2021Review
- Therapeutic strategies of different HPV status in Head and Neck Squamous Cell Carcinoma.International journal of biological sciences · 2021Review
- Carbon Ion Radiobiology.Cancers · 2020Review
- The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.Scientific reports · 2020Article
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22 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPre-clinically, phosphoinositide 3-kinase (PI3K) inhibition radiosensitises tumours by increasing intrinsic radiosensitivity and by reducing tumour hypoxia. We assessed whether buparlisib, a class 1 PI3K inhibitor, can be safely combined with radiotherapy in patients with non-small cell lung carcinoma (NSCLC) and investigated its effect on tumour hypoxia.
methodsThis was a 3 + 3 dose escalation and dose expansion phase I trial in patients with advanced NSCLC. Buparlisib dose levels were 50 mg, 80 mg and 100 mg once daily orally for 2 weeks, with palliative thoracic radiotherapy (20 Gy in 5 fractions) delivered during week 2. Tumour hypoxic volume (HV) was measured using
resultsTwenty-one patients were recruited with 9 patients evaluable for maximum tolerated dose (MTD) analysis. No dose-limiting toxicity was reported; therefore, 100 mg was declared the MTD, and 10 patients received this dose in the expansion phase. Ninety-four percent of treatment-related adverse events were ≤grade 2 with fatigue (67%), nausea (24%) and decreased appetite (19%) most common per patient. One serious adverse event (grade 3 hypoalbuminaemia) was possibly related to buparlisib. No unexpected radiotherapy toxicity was reported. Ten (67%) of 15 patients evaluable for imaging analysis were responders with 20% median reduction in HV at the MTD.
conclusionThis is the first clinical trial to combine a PI3K inhibitor with radiotherapy in NSCLC and investigate the effects of PI3K inhibition on tumour hypoxia. This combination was well tolerated and PI3K inhibition reduced hypoxia, warranting investigation into whether this novel class of radiosensitisers can improve radiotherapy outcomes.
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