Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy: baseline results from the HOLISTIC study.

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher's exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care.

Quantification of sunitinib and N-desethyl sunitinib in human EDTA plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry: validation and application in routine therapeutic drug monitoring.

BACKGROUND: Given the low therapeutic index, the large interindividual variability in systemic exposure and the positive exposure-efficacy relationship of sunitinib, there is a rationale for therapeutic drug monitoring (TDM) of sunitinib. To support TDM, a method for determination of sunitinib and its active metabolite (N-desethyl sunitinib) has been developed and validated. METHODS: For determination of sunitinib and N-desethyl sunitinib in human EDTA plasma samples, high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used. Validation experiments according to Food and Drug Administration guidelines were performed. In addition, the results of 25 analytical runs with 58 patient samples using 8 calibrators and 3 levels of quality control (QC) samples per analysis were compared with the results of analyses using only 3 calibrators and 1 QC sample to accelerate sample turnaround time. The method comparison experiment was performed according to international guidelines. RESULTS: The HPLC-MS/MS method was validated over a linear range from 2.5 to 500 ng/mL using 50 µL plasma volumes, with good intra- and interassay accuracy and precision. In addition, the mean of the absolute differences between the compared methods was only -0.66 ng/mL (mean of relative differences, -0.85%), which is not a clinically relevant difference. CONCLUSIONS: This method has been applied successfully for routine TDM purposes for patients treated with sunitinib. Moreover, reliable results with a rapid turnaround time were obtained when performing a short analytical run containing only 3 calibrators and 1 QC sample.