Dose-limiting Urinary Toxicity With Pembrolizumab Combined With Weekly Hypofractionated Radiation Therapy in Bladder Cancer.
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Date
2018-08-01Author
Tree, AC
Jones, K
Hafeez, S
Sharabiani, MTA
Harrington, KJ
Lalondrelle, S
Ahmed, M
Huddart, RA
Type
Journal Article
Metadata
Show full item recordAbstract
There is currently significant interest in the potential benefits of combining radiation and immune checkpoint blockade (ICB) to stimulate both regional and distant abscopal immune responses. In melanoma and lung cancer, patients who have received radiation therapy during ICB appear to have prolonged survival. The PLUMMB trial (Pembrolizumab in Muscle-invasive/Metastatic Bladder cancer) (NCT02560636) is a phase I study to test the tolerability of a combination of weekly radiation therapy with pembrolizumab in patients with metastatic or locally advanced urothelial cancer of the bladder. In the first dose-cohort, patients received pembrolizumab 100 mg 3-weekly, starting 2 weeks before commencing weekly adaptive bladder radiation therapy to a dose of 36 Gy in 6 fractions. The first dose-cohort was stopped after 5 patients, having met the predefined definition of dose-limiting toxicity. Three patients experienced grade 3 urinary toxicities, 2 of which were attributable to therapy. One patient experienced a grade 4 rectal perforation. In view of these findings, the trial has been paused and the protocol will be amended to reduce radiation therapy dose per fraction. The authors advise caution to those combining radiation therapy and ICB, particularly when radiation therapy is given at high dose per fraction for pelvic tumours. The PLUMMB trial met the protocol-defined definition of dose-limiting toxicity and will be amended to reduce radiation therapy dose.
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Subject
Humans
Neoplasm Metastasis
Disease Progression
Immunotherapy
Combined Modality Therapy
Cohort Studies
Radiometry
Radiation Dosage
Maximum Tolerated Dose
Urinary Bladder
Urinary Bladder Neoplasms
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Radiation Dose Hypofractionation
Research team
Clinical Academic Radiotherapy (Huddart)
Gynaecological Cancer
Lung Radiotherapy
Targeted Therapy
Language
eng
Date accepted
2018-04-24
License start date
2018-08
Citation
International journal of radiation oncology, biology, physics, 2018, 101 (5), pp. 1168 - 1171
Publisher
ELSEVIER SCIENCE INC