Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study
Background and purpose: Radical concurrent chemoradiotherapy (CRT) for oesophageal cancer is associated with significant morbidity and is unsuitable for some patients. Olaparib, an inhibitor of the DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) has radiosensitising properties and may be bette...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405630823000393 |
| _version_ | 1797838604404260864 |
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| author | Hamid Sheikh David Ryder Andrew Bateman Anthony Chalmers Andrew Jackson |
| author_facet | Hamid Sheikh David Ryder Andrew Bateman Anthony Chalmers Andrew Jackson |
| author_sort | Hamid Sheikh |
| collection | DOAJ |
| description | Background and purpose: Radical concurrent chemoradiotherapy (CRT) for oesophageal cancer is associated with significant morbidity and is unsuitable for some patients. Olaparib, an inhibitor of the DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) has radiosensitising properties and may be better tolerated than chemotherapy. Materials and methods: We performed a phase 1 study of olaparib with radiotherapy (RT) in oesophageal cancer patients unsuitable for conventional CRT to determine its maximum tolerated dose (MTD) in this setting. Results: Eight patients were recruited. One of 5 patients receiving olaparib 50 mg twice daily and two of 3 receiving 100 mg twice daily experienced dose limiting toxicity (DLT). Conclusions: Olaparib 100 mg twice daily exceeded the MTD in combination with RT in these patients. 50 mg twice daily may be the MTD but this cannot be stated with certainty as the study closed before full recruitment. |
| first_indexed | 2024-04-09T15:43:30Z |
| format | Article |
| id | doaj.art-cf4a84c75990477593f9349e5ae34015 |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-04-09T15:43:30Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-cf4a84c75990477593f9349e5ae340152023-04-27T06:06:33ZengElsevierClinical and Translational Radiation Oncology2405-63082023-05-0140100614Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I studyHamid Sheikh0David Ryder1Andrew Bateman2Anthony Chalmers3Andrew Jackson4The Christie NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UKManchester Clinical Trials Unit, University of Manchester, Oxford Road, Manchester M13 9PL, UKUniversity Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UKWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, Garscube Estate, Glasgow G61 1QH, UKUniversity Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Corresponding author at: Department of Clinical Oncology, Mailpoint 301, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.Background and purpose: Radical concurrent chemoradiotherapy (CRT) for oesophageal cancer is associated with significant morbidity and is unsuitable for some patients. Olaparib, an inhibitor of the DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) has radiosensitising properties and may be better tolerated than chemotherapy. Materials and methods: We performed a phase 1 study of olaparib with radiotherapy (RT) in oesophageal cancer patients unsuitable for conventional CRT to determine its maximum tolerated dose (MTD) in this setting. Results: Eight patients were recruited. One of 5 patients receiving olaparib 50 mg twice daily and two of 3 receiving 100 mg twice daily experienced dose limiting toxicity (DLT). Conclusions: Olaparib 100 mg twice daily exceeded the MTD in combination with RT in these patients. 50 mg twice daily may be the MTD but this cannot be stated with certainty as the study closed before full recruitment.http://www.sciencedirect.com/science/article/pii/S2405630823000393Oesophageal cancerOlaparibPARP inhibitorRadiotherapyRadiosensitiser |
| spellingShingle | Hamid Sheikh David Ryder Andrew Bateman Anthony Chalmers Andrew Jackson Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study Clinical and Translational Radiation Oncology Oesophageal cancer Olaparib PARP inhibitor Radiotherapy Radiosensitiser |
| title | Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study |
| title_full | Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study |
| title_fullStr | Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study |
| title_full_unstemmed | Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study |
| title_short | Radiotherapy and olaparib in combination for carcinoma of the oesophagus: A phase I study |
| title_sort | radiotherapy and olaparib in combination for carcinoma of the oesophagus a phase i study |
| topic | Oesophageal cancer Olaparib PARP inhibitor Radiotherapy Radiosensitiser |
| url | http://www.sciencedirect.com/science/article/pii/S2405630823000393 |
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