Sabine Visser

Reliability and validity of the Cancer Therapy Satisfaction Questionnaire in lung cancer

PurposeTo test the reliability and validity of the Cancer Treatment Satisfaction Questionnaire (CTSQ), to assess its relation with quality of life (QoL), and to assess the interpretability of the domain scores in lung cancer patients receiving intravenous chemotherapy.MethodsPatients with stage IIIB and IV non-squamous non-small cell lung carcinoma treated with pemetrexed were enrolled in our study. They completed the 16-item CTSQ and two other (health-related) QoL questionnaires. Information about sociodemographic characteristics, cancer stage, and the experience of adverse events was collected. Internal consistency, construct validity, and clinical interpretability were calculated.ResultsFifty-five patients completed the CTSQ. Correlations of the CTSQ items with its domain were all above 0.40. A high correlation between item 8 and the expectations of therapy and satisfaction with therapy domain was observed (0.50 and 0.48, respectively). The CTSQ domains demonstrated good internal consistency and low to moderate correlations of the CTSQ with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and World Health Organization Quality of Life-BREF. No significant differences in mean domain scores were observed in relation to the number and severity of different adverse events and chemotherapy-related adverse events.ConclusionsThe Dutch version of the CTSQ was found to be a reliable and valid instrument to assess satisfaction and expectations of treatment in lung cancer patients receiving intravenous chemotherapy. Furthermore, the CTSQ proved to be of additional informative value as not all of its domains correlated with the various domains of the existing HRQoL instruments.

160P: Depressive symptoms, performance score, and personality traits as predictors of (health related) quality of life in patients with advanced stage lung cancer

whereas CT showed a high specificity (Table 1). PET parameters (max and peak SUV) reached a significant AUC to predict RECIST analysis. Conclusions: The higher number of PET responders combined with the higher AUC values compared to CT indicates that PET is able to predict treatment response earlier than CT, though typically at a lower specificity. The next step will be to define the optimal thresholds for better response prediction including the combination of PET-based and CT-based criteria together with clinical variables. Clinical trial identification: NCT01171170 Legal entity responsible for the study: A.-M. C. Dingemans Funding: Dutch Cancer Society Disclosure: All authors have declared no conflicts of interest.

187P: Patient's feelings about side-effects are predictive for (Health Related) Quality of Life in patients with advanced stage lung cancer treated with chemotherapy

different from frontline therapy. We analyzed safety and tolerability as well as number of Bev cycles given to these cohort. Results: Nine pts received C/P/Bev and 3 pts received C/Pem/Bev followed by maintenance (MTX) Bev. Median age was 77 years old (range, 75–82); 9 (75%) pts were female; all pts had adenocarcinoma histology. Most common AEs were: fatigue (n = 4), vomiting (n = 2), and diarrhea (n = 2). Only one pt stopped Bev due to SAEs (hypertensive crisis); no embolic events, nephrotic syndrome, gastrointestinal perforation, fistula perforation, RPLS, and serious hemorrhage were found. Median cycles of MTX Bev was 4.5 (range, 0–28); median total of Bev cycles including induction was 9.5 (range, 1–32). Median progression-free survival (PFS) was 7.1 months. Conclusions: In our 12 pts older than 75 years old, we did not find major SAEs secondary to Bev but 1 pt. Our pts had good ECOG PS and 8 pts (75%) had 1 comorbid condition. Median PFS was similar to that reported in the literature when Bev has been combined with platinum-based doublet followed by MTX. With a detailed clinical history and careful assessment, our experience indicates that Bev can be offered to elderly pts older than 75 years old. Legal entity responsible for the study: Lynn Cancer Institute Research Department Funding: Lynn Cancer Institute Research Department Disclosure: E.S. Santos: Speaker Bureau: Genentech, Lilly US Oncology. All other authors have declared no conflicts of interest.

A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites

Currently no quantification method exists for potentially therapeutically relevant polyglutamate metabolites of the drug pemetrexed which is used for the treatment of lung carcinoma patients. We developed and tested an LC-MS/MS-based analytical assay that uses isotope-labeled internal standards to quantify pemetrexed and its (poly)glutamate metabolites in clinical human plasma samples of lung carcinoma patients. UHPLC chromatography and triple quadrupole mass spectrometry showed an LLOQ of 0.2nmol/L for pemetrexed and an LLOQ of 0.5nmol/L for the two metabolites (one glutamate and two glutamate moieties covalently bound to the pemetrexed molecule, for which no other quantification methods have previously been published). The recoveries for PMTX and its metabolites ranged between 30% and 67%. Precision and accuracy at a concentration of 20nmol/L for all four analytes was well below 15% CV. The precision (RSD) in the biological replicates of the separate days (within-run precision) as well as the reproducibility over several days (between-run precision), tested in the range of 5-250nmol/L, were all below 15%. Autosampler, benchtop and freeze-thaw cycle stability of the analytes was also demonstrated. To illustrate the new assay in a relevant biological context, concentrations of pemetrexed and the two metabolites were quantified in plasma samples of lung carcinoma patients treated with pemetrexed. The assay is straightforward, relatively easy to perform, and has potential for use in therapeutic drug monitoring in non-small cell lung carcinoma patients.

High and individually variable enzymatic activity precludes accurate determination of pemetrexed, methotrexate and their polyglutamate metabolite concentrations in plasma

HighlightsProtease degradation of polyglutamated molecules in plasma is very fast.Protease degradation of polyglutamated molecules is variable between individuals.Polyglutamates of pemetrexed and of methotrexate are both affected.This metabolism has serious consequences for quantification studies. ABSTRACT Most drugs are metabolized in the human body. Therefore, it is essential for therapeutic drug monitoring studies to also take into account the concentrations of drug metabolites. One of the possible metabolic activities on drugs such as pemetrexed or methotrexate is (poly)glutamation. Here, we report on a series of experiments that we performed to investigate the stability of polyglutamate metabolites in plasma. Removal of glutamate residues from pemetrexed polyglutamate by most likely proteases in human plasma is influenced by temperature as it is observed at 25 °C and even more strongly at 37 °C, but not at 4 °C. The observed protease activity is highly variable among patients; in approximately 15–20% of the patients tested it is not observed, whereas in other individuals the activity is so extensive that after 10 min, more than 50% of spiked polyglutamated pemetrexed is degraded at room temperature (5–10% of the tested individuals). Similar observations also pertain to methotrexate polyglutamates. These observations do not extend to pemetrexed and methotrexate themselves which are unaffected by this activity. Due to the considerable and, among individuals, variable protease activities on polyglutamated drug metabolites in plasma, these metabolites are virtually impossible to quantify if no precautions are taken.

Renal impairment during pemetrexed maintenance in patients with advanced non-small-cell lung cancer: a cohort study

Optimal survival benefit from different lines of anticancer treatment in advanced nonsmall cell lung cancer (NSCLC) requires conservation of renal function. We evaluated the development of renal impairment during pemetrexed maintenance. In a prospective multicentre cohort study, we evaluated the incidence of acute/chronic kidney disease (AKD/CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with pemetrexed maintenance. We validated the findings in an independent cohort. 190 patients received pemetrexed. In the primary cohort, 149 patients started induction, of whom 44 patients (30%) continued maintenance. In the independent cohort, 41 patients received maintenance. During maintenance 13 patients (30%) developed AKD, leading to CKD and treatment discontinuation in eight patients (62%) in the primary cohort. Higher estimated glomerular filtration rate (eGFR) (per unit 5 mL·min−1 per 1.73 m2) before maintenance and induction (OR 0.70, 95% CI 0.54–0.90 and OR 0.78, 95% CI 0.62–0.98, respectively) and relative decline (per 10%) in eGFR during induction (OR 2.54, 95% CI 1.36–4.74) were associated with AKD during maintenance. In the independent cohort, 20 patients (49%) developed AKD, leading to CKD in 11 patients (55%) and treatment discontinuation in six patients (30%). Patients are at risk for renal impairment during pemetrexed maintenance, which may jeopardise further lines of anticancer treatment. There is a significant risk of renal impairment during pemetrexed maintenance, which may jeopardise further treatment http://ow.ly/q8r830lnNZR

Treatment Satisfaction of Patients With Advanced Non–Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL)

&NA; To gain insight into the patient‐centered value of treatment harms and benefits, we prospectively evaluated the satisfaction with therapy (SWT) in patients with advanced non–small‐cell lung cancer undergoing chemotherapy. Our results showed that SWT covers different aspects of patient‐reported impact of the effect of treatment than quality of life and adverse events. Therefore, SWT could be useful in clinical decision‐making. Introduction: In patients with advanced non–small‐cell lung cancer, the treatment benefits and risks need to be constantly weighed. We explored patient‐reported satisfaction with therapy (SWT) and assessed its value in addition to quality of life (QoL) and adverse events (AEs). Patients and Methods: In a prospective multicenter cohort study, patients with stage IIIB/IV non–small‐cell lung cancer received platinum‐pemetrexed chemotherapy. They completed the World Health Organization Quality of Life‐BREF (WHOQoL‐BREF) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) before and during chemotherapy. After the last cycle, patients reported on SWT, expectations of therapy, and feelings about side effects (FSE) using the Cancer Therapy Satisfaction Questionnaire. The explained variance (R2) of QoL after treatment by SWT was calculated. Using multivariable linear regression, we examined the association of SWT with patient‐ and treatment‐related variables, FSE, and AEs. Results: Eighty‐nine patients finished 4 cycles of chemotherapy, 65 of whom completed the Cancer Therapy Satisfaction Questionnaire. Fifty‐six patients (86.2%) would probably or definitely decide to undergo the same treatment again, regardless of deterioration or improvement in QoL or a high or low frequency of AEs during chemotherapy. The explained variance of QoL by SWT was greatest for the EORTC QLQ C‐30 global health status/QoL scale (R2 = 0.170). Patient age (&bgr; = 0.43; 95% confidence interval [CI], 0.05‐0.82), FSE (&bgr; = 0.17; 95% CI, 0.06‐0.29), and tumor response (&bgr; = 7.93; 95% CI (1.64 to 14.22)) were independently associated with SWT. Conclusion: SWT could provide important supplementary information in addition to QoL assessments and treatment toxicities. Tumor response, older age, and FSE score were associated with better SWT. These insights could affect decision‐making during palliative chemotherapy.