Central venous access related adverse events after trabectedin infusions in soft tissue sarcoma patients; experience and management in a nationwide multi-center study.
BACKGROUND
Trabectedin has shown efficacy against soft tissue sarcomas (STS) and has manageable toxicity. Trabectedin is administered through central venous access devices (VAD), such as subcutaneous ports with tunneled catheters, Hickman catheters and PICC lines. Venous access related adverse events are common, but have not yet been reported in detail.


METHODS
A retrospective analysis of patient files of STS patients receiving trabectedin monotherapy between 1999 and 2014 was performed in all five STS referral centers in the Netherlands. This survey focused on adverse events related to the VAD and the actions taken in response to these events.


RESULTS
In the 127 patients included in this analysis, 102 venous access ports (VAP), 15 Hickman catheters and 10 PICC lines were used as primary means of central venous access. The most frequently reported adverse events at the VAD site were erythema (30.7%), pain (28.3%), inflammation (11.8%) and thrombosis (11.0%). Actions taken towards these adverse events include oral antibiotics (17.3%), VAD replacement (15.0%) or a wait-and-see policy (13.4%). In total, 45 patients (35.4%) with a subcutaneous port developed a varying degree of inflammation along the trajectory of the tunneled catheter. In all but three patients, this was a sterile inflammation, which was considered a unique phenomenon for trabectedin. Microscopic leakage of trabectedin along the venous access device and catheter was considered the most plausible cause for this adverse event. Placing the catheter deeper under the skin resolved the issue almost completely.


CONCLUSIONS
Trabectedin infusion commonly leads to central venous access related adverse events. Sterile inflammation along the catheter trajectory is one of the most common adverse events and can be prevented by placing the catheter deeper under the skin.
Department of Medical Oncology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.
Michiel C
MC
Verboom
Department of Medical Oncology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.
Jan
J
Ouwerkerk
Department of Medical Oncology, Antoni van Leeuwenhoek-Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, The Netherlands.
Neeltje
N
Steeghs
Department of Radiology, Interventional Radiology Section, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.
Jacob
J
Lutjeboer
Department of Medical Oncology, Antoni van Leeuwenhoek-Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, The Netherlands.
J
J
Martijn Kerst
Department of Medical Oncology, Radboud University Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands.|The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP UK.
Winette T A
WTA
van der Graaf
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Postbus 30.001, 9700 RB Groningen, The Netherlands.
Anna K L
AKL
Reyners
Department of Medical Oncology, Erasmus MC Cancer Institute, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
Stefan
S
Sleijfer
Department of Medical Oncology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.
Hans
H
Gelderblom
Adverse events; Central venous catheters; Soft tissue sarcoma; Trabectedin