RESUMEN
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. CONCLUSION: 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.
RESUMEN
BACKGROUND: Low trough imatinib concentration (C min) values have been associated with poor clinical outcomes in gastrointestinal stromal tumour (GIST) patients. This study describes the pharmacokinetics of imatinib in a large cohort of GIST patients in routine clinical care. METHODS: An observational study was performed in imatinib-treated GIST patients. Patient and tumour characteristics were derived from the Dutch GIST Registry and medical records. Imatinib concentrations were measured by liquid chromatography with tandem mass spectrometry. The analyses included the occurrence of a low imatinib C min (<1000 µg/L), the change in the C min over time and the correlation between exposure and response. RESULTS: In total, 421 plasma samples were available from 108 GIST patients. Most patients (79.6 %) received an imatinib dose of 400 mg. The inter- and intrapatient variabilities in C min were 54 and 23 %, respectively. In the first steady-state sample, 44.4 % of patients presented with C min values <1000 µg/L; 32.4 % of patients had values <1000 µg/L in >75 % of their samples. Only 33.3 % of patients had C min values ≥1000 µg/L in all measured samples. No decrease in C min over time was found (P > 0.05). Fifty-seven (91.9 %) of 62 palliative-treated patients had a tumour response (median C min 1271 µg/L). Five palliative patients (8.1 %) did not respond (median C min 920 µg/L). Given the limited number of non-responders in this cohort, no statistically significant association with clinical benefit could be demonstrated. CONCLUSION: In routine clinical care, one third of GIST patients are systematically underexposed with a fixed dose of imatinib. Prospective clinical studies are needed to investigate the value of C min-guided imatinib dosing in GIST patients.