Temoporfin-mediated photodynamic therapy for advanced, incurable head and neck cancer: a multicenter study

Background: The aim of this multicenter study was to confirm the antitumor efficacy of Foscan®-mediated photodynamic therapy (PDT) in patients with advanced, end-stage head and neck squamous cell carcinoma (HNSCC). Methods: Thirty-nine patients with HNSCC lesions ≤ 10 mm in depth, recurring following standard treatment, were intravenously injected with Foscan®, followed 96 hours later by illumination of the tumor surface with 652 nm laser light. Tumor response was assessed on an intent-to-treat basis using World Health Organization (WHO) criteria. Results: Of 39 treated patients 19 obtained a complete response (CR), 2 a partial response (PR), 5 a stable disease (SD) for at least 8 weeks, 5 patients had progressive disease (PD) and 8 patients were non-evaluable (NE). Thus, in the per-protocol analysis 68% of the patients obtained an objective tumor response (CR: 61%, PR: 6.5%). Of the treated patients 54% [95% CI: 37%; 70%] showed an objective tumor response (CR 49%). Median survival was significantly longer for responders (160 weeks) than for non-responders (32 weeks). No major toxicities were observed. Conclusions: Patients with advanced head and neck cancer with lesions ≤ 10 mm in depth, who have exhausted other treatment options, can achieve significant local control and survival benefit from Foscan®-mediated PDT. As opposed to conventional treatment modalities, this treatment is tolerated wellstatus: publishe

Potentially clinically relevant concentrations of Cefazolin, Midazolam, Propofol, and Sufentanil in auto-transfused blood in congenital cardiac surgery

Abstract Background Use of donor blood in congenital cardiac surgery increases the risk for post-operative morbidity and mortality. To reduce the need for allogenic blood transfusion a technique for peri-operative mechanical red cell salvage is applied. Blood from the operation site is collected in a reservoir, processed, passed through a lipophilic filter and returned to the patient. Influence of this cellsaver system on coagulation, fibrinolysis and inflammatory markers is known. To our knowledge no studies have been performed on the effects of autotransfusion on drug concentrations. A clinically relevant drug dose could potentially be returned to the patient through the auto-transfused blood, leading to unwanted drug reactions post-operatively. We aimed to measure drug concentrations in blood salvaged from the operation site and in the auto-transfused blood to determine if a clinically relevant drug dose is returned to the patient. Methods The study was performed at the Department of Cardiothoracic Surgery of a tertiary university hospital. Blood samples were taken from the reservoir, after processing before the lipophilic filter, the auto-transfused blood, and the waste fluid. Samples were stored at − 80 C and drug concentration for sufentanil, propofol, midazolam and cefazolin were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Drug concentrations measured in the reservoir and the auto-transfused blood were compared and the relative reduction was calculated for each patient. Results Blood samples were taken from 18 cellsaver runs in 18 patients, age 0–13 years. Drug concentrations in the reservoir were comparable to concomitant concentrations in the patient. For sufentanil 34% (median, IQR 27–50) of drug concentration was retained from the reservoir in the auto-transfused blood, for midazolam 6% (median, IQR 4–10), for cefazolin 5% (median, IQR 2–6) and for propofol 0% (median, IQR 0–0) respectively. Conclusion Depending on the drug, up to 34% of the drug concentration salvaged from the operation site is returned to the patient through autotransfusion, potentially causing unwanted drug reactions post-operatively. Additionally, influence of a cellsaver system should be considered in pharmacological research during and after congenital cardiac surgery and could result in dose adjustments in the postoperative phase. Trial registration Registration at the Dutch Trial Registry (NTR3579) at August 14 2012