dc.contributor.author | Nimalasena, S | |
dc.contributor.author | Gothard, L | |
dc.contributor.author | Anbalagan, S | |
dc.contributor.author | Allen, S | |
dc.contributor.author | Sinnett, V | |
dc.contributor.author | Mohammed, K | |
dc.contributor.author | Kothari, G | |
dc.contributor.author | Musallam, A | |
dc.contributor.author | Lucy, C | |
dc.contributor.author | Yu, S | |
dc.contributor.author | Nayamundanda, G | |
dc.contributor.author | Kirby, A | |
dc.contributor.author | Ross, G | |
dc.contributor.author | Sawyer, E | |
dc.contributor.author | Castell, F | |
dc.contributor.author | Cleator, S | |
dc.contributor.author | Locke, I | |
dc.contributor.author | Tait, D | |
dc.contributor.author | Westbury, C | |
dc.contributor.author | Wolstenholme, V | |
dc.contributor.author | Box, C | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | Yarnold, J | |
dc.contributor.author | Somaiah, N | |
dc.date.accessioned | 2020-06-23T10:27:35Z | |
dc.date.issued | 2020-11-15 | |
dc.identifier.citation | International journal of radiation oncology, biology, physics, 2020, 108 (4), pp. 1019 - 1029 | |
dc.identifier.issn | 0360-3016 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3772 | |
dc.identifier.eissn | 1879-355X | |
dc.identifier.doi | 10.1016/j.ijrobp.2020.06.022 | |
dc.description.abstract | PURPOSE: Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. METHODS AND MATERIALS: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis. RESULTS: Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1β, IL-4, and MIP-1α with tumor response. CONCLUSIONS: Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor. | |
dc.format | Print-Electronic | |
dc.format.extent | 1019 - 1029 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-06-12 | |
rioxxterms.versionofrecord | 10.1016/j.ijrobp.2020.06.022 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of radiation oncology, biology, physics | |
pubs.issue | 4 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy/Breast Cancer Radiotherapy (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Breast Cancer Radiotherapy/Breast Cancer Radiotherapy (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 108 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Breast Cancer Radiotherapy | |
icr.researchteam | Pre-Clinical MRI | |
icr.researchteam | Translational Breast Radiobiology | |
dc.contributor.icrauthor | Gothard, Lone | |
dc.contributor.icrauthor | Anbalagan, Selvakumar | |
dc.contributor.icrauthor | Box, Carol | |
dc.contributor.icrauthor | Robinson, Simon | |
dc.contributor.icrauthor | Yarnold, John | |
dc.contributor.icrauthor | Somaiah, Navita | |