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A phase 1 ‘window-of-opportunity’ trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma…

Overview of attention for article published in BMC Cancer, August 2016
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Title
A phase 1 ‘window-of-opportunity’ trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma patients
Published in
BMC Cancer, August 2016
DOI 10.1186/s12885-016-2709-z
Pubmed ID
Authors

Ruben T. H. M. Larue, Lien Van De Voorde, Maaike Berbée, Wouter J. C. van Elmpt, Ludwig J. Dubois, Kranthi M. Panth, Sarah G. J. A. Peeters, Ann Claessens, Wendy M. J. Schreurs, Marius Nap, Fabiënne A. R. M. Warmerdam, Frans L. G. Erdkamp, Meindert N. Sosef, Philippe Lambin

Abstract

Neo-adjuvant chemoradiotherapy followed by surgery is the standard treatment with curative intent for oesophageal cancer patients, with 5-year overall survival rates up to 50 %. However, patients' quality of life is severely compromised by oesophagectomy, and eventually many patients die due to metastatic disease. Most solid tumours, including oesophageal cancer, contain hypoxic regions that are more resistant to chemoradiotherapy. The hypoxia-activated prodrug evofosfamide works as a DNA-alkylating agent under these hypoxic conditions, which directly kills hypoxic cancer cells and potentially minimizes resistance to conventional therapy. This drug has shown promising results in several clinical studies when combined with chemotherapy. Therefore, in this phase I study we investigate the safety of evofosfamide added to the chemoradiotherapy treatment of oesophageal cancer. A phase I, non-randomized, single-centre, open-label, 3 + 3 trial with repeated hypoxia PET imaging, will test the safety of evofosfamide in combination with neo-adjuvant chemoradiotherapy in potentially resectable oesophageal adenocarcinoma patients. Investigated dose levels range from 120 mg/m2 to 340 mg/m2. Evofosfamide will be administered one week before the start of chemoradiotherapy (CROSS-regimen) and repeated weekly up to a total of six doses. PET/CT acquisitions with hypoxia tracer (18)F-HX4 will be made before and after the first administration of evofosfamide, allowing early assessment of changes in hypoxia, accompanied with blood sampling to measure hypoxia blood biomarkers. Oesophagectomy will be performed according to standard clinical practice. Higher grade and uncommon non-haematological, haematological, and post-operative toxicities are the primary endpoints according to the CTCAEv4.0 and Clavien-Dindo classifications. Secondary endpoints are reduction in hypoxic fraction based on (18)F-HX4 imaging, pathological complete response, histopathological negative circumferential resection margin (R0) rate, local and distant recurrence rate, and progression free and overall survival. This is the first clinical trial testing evofosfamide in combination with chemoradiotherapy. The primary objective is to determine the dose limiting toxicity of this combined treatment and herewith to define the maximum tolerated dose and recommended phase 2 dose for future clinical studies. The addition of non-invasive repeated hypoxia imaging ('window-of-opportunity') enables us to identify the biologically effective dose. We believe this approach could also be used for other hypoxia targeted drugs. ClinicalTrials.gov Identifier: NCT02598687 .

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 74 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 74 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 18%
Student > Bachelor 11 15%
Student > Master 11 15%
Other 6 8%
Student > Ph. D. Student 6 8%
Other 13 18%
Unknown 14 19%
Readers by discipline Count As %
Medicine and Dentistry 30 41%
Biochemistry, Genetics and Molecular Biology 5 7%
Nursing and Health Professions 5 7%
Immunology and Microbiology 2 3%
Sports and Recreations 2 3%
Other 12 16%
Unknown 18 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2016.
All research outputs
#7,133,944
of 8,247,986 outputs
Outputs from BMC Cancer
#2,810
of 3,471 outputs
Outputs of similar age
#214,328
of 253,918 outputs
Outputs of similar age from BMC Cancer
#179
of 253 outputs
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