Evaluation of the Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity After Brachytherapy of Liver Metastases From Colorectal Carcinoma, Assessed in a Prospective Randomised Trial
A preventive effect of pentoxifylline, ursodeoxycholic acid and low dose low molecular
weight heparin on pathological processes in healthy tissue after irradiation is described in
clinical studies on percutaneous liver irradiation and on bone marrow transplantation.
However, data remains inconclusive.
This exploratory study aims at assessing whether a protective effect of the combination of
pentoxifylline, ursodeoxycholic acid and enoxaparin can be demonstrated in a limited number
of patients with liver metastases of colorectal cancer after HDR brachytherapy.
All patients receive a single fraction CT/MRI-guided HDR-brachytherapy of colorectal liver
metastases using Iridium-192 as a standard therapy. The follow-up consists of 4 MRI controls
of the abdomen using the hepatocyte-specific contrast agent Gd-EOB-DTPA (Primovist) after 3
days, 6 weeks, 3 months and 6 months as well as blood samples and a questionnaire taken the
same time.Within the study, 22 patients are given low dose low molecular weight heparin,
pentoxifylline and ursodeoxycholic acid for 8 weeks starting with the preinterventional day.
Another 22 patient will receive the standard therapy without the medication. After
completion of the follow-up, MRI volume data of the lesion will be acquired and compared to
the dosimetric treatment plan. Blood samples are tested for liver-specific and inflammatory
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
HDR-brachytherapy isodose (measured in Gy) that corresponds to the metastases without enhancement of Gd-EOB-DTPA in MR imaging using an axial T1 THRIVE sequence.
The primary variable is the HDR-brachytherapy isodose that encloses liver tissue with a diminished uptake of the hepatocyte selective contrast agent GD-EOB-DTPA. By identifying the damaged volume in every layer of the axial T1 THRIVE image, 3D data can be calculated and correlated to a specific isodose when merged with the 3D irradiation treatment plan. Prior to brachytherapy, the baseline volume of the metastases will be measured instead of the liver tissue damaged by irradiation.
One day prior to brachytherapy.
Jens Ricke, MD
University of Magdeburg, Faculty for Medicine
Germany: Federal Institute for Drugs and Medical Devices