Discussion
nausea, liver dysfunction, veno-occlusive disease, abdominal pain, liver malignancies, peripheral artery disease, colorectal liver metastases
PERIPHERAL ARTERY DISEASE, VENO-OCCLUSIVE DISEASE, ADVERSE EVENTS, SOLID TUMORS, METASTASES
As the radiation tolerance of healthy liver parenchyma is a limiting factor of ablative radiation therapies (e.g., interstitial brachytherapy or stereotactic body radiotherapy) targeting liver malignancies, a medication-based increment of hepatic tolerance doses might play a substantial role to increase dose delivery to the target volume.In a prior study, we investigated ursodeoxycholic acid (UDCA), pentoxifylline (PTX) and low molecular weight heparin (LMWH) administered for 8 weeks in patients undergoing interstitial brachytheraphy (iBT) of colorectal liver metastases (Seidensticker et al. Here, we encountered an unexpected accumulation of adverse events arising typically within one week after initiation of medication attributed to PTX (e.g., nausea up to 30% and abdominal pain up to 35% of patients) which resolved within two days after discontinuation and did not require additional medication. As side effects of UDCA only include alteration of stool quality and no interactions with PTX are assumable according to the pharmacological properties, a cumulative effect of both drugs is unlikely.Although the number of patients in the recent study is low, a total of eight different conditions (all known to be side effects of PTX) were recorded and frequencies were at least two time above the expected frequency (according to SmPC) in six of them (SmPC Trental In total, susceptibility to side effects of PTX may be increased in patients with metastases of solid tumors which should be regarded as a cohort at risk compared to patients with peripheral artery disease (regular indication of PTX). Possible explanations of these findings might include prior history of chemotherapy or concomitant interstitial brachytherapy while no similar reports can be found in the literature on bone marrow transplantation (Beelen et al. As a consequence, only 8 out of 16 patients in the investigative arm were included in the per-protocol analysis which could not demonstrate the expected effect of PTX and UDCA on radiation-induced liver dysfunction. Beside the small number of eligible patients resulting in a low statistical power, reduction of the combination treatment by LMWH must be assumed to have contributed to the negative outcome of our study.Investigational drugs potentially preventing fRILI still originate from studies of veno-occlusive disease in the setting of bone marrow transplantation (included whole-body irradiation in the conditioning regimen) (Attal et al. 