Implications of subcutaneous or intravenous delivery of trastuzumab: further insight from patient interviews in the PrefHer study

BACKGROUND: The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. METHODS: The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. RESULTS: 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). CONCLUSIONS: Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. EUDRACT NUMBER: 2010-024099-25

Ranking commercial machines through data transposition

The performance numbers reported by benchmarking consortia and corporations provide little or no insight into the performance of applications of interest that are not part of the benchmark suite. This paper describes data transposition, a novel methodology for addressing this ubiquitous benchmarking problem. Data transposition predicts the performance for an application of interest on a target machine based on its performance similarities with the industry-standard benchmarks on a limited number of predictive machines. The key idea of data transposition is to exploit machine similarity rather than workload similarity as done in prior work, i.e., data transposition identifies a predictive machine that is most similar to the target machine of interest for predicting performance for the application of interest. We demonstrate the accuracy and effectiveness of data transposition using the SPEC CPU2006 benchmarks and a set of 117 commercial machines. We report that the machine ranking obtained through data transposition correlates well with the machine ranking obtained using measured performance numbers (average correlation coefficient of 0.93). Not only does data transposition improve average correlation, we also demonstrate that data transposition is more robust towards outlier benchmarks, i.e., the worst-case correlation coefficient improves from 0.59 by prior art to 0.71. More concretely, using data transposition to predict the top-1 machine for an application of interest leads to the best performing machine for most workloads (average deficiency of 1.2% and max deficiency of 24.8% for one benchmark), whereas prior work leads to deficiencies over 100% for some workloads

Modelling chemotherapy resistance in palliation and failed cure

The goal of palliative cancer chemotherapy treatment is to prolong survival and improve quality of life when tumour eradication is not feasible. Chemotherapy protocol design is considered in this context using a simple, robust, model of advanced tumour growth with Gompertzian dynamics, taking into account the effects of drug resistance. It is predicted that reduced chemotherapy protocols can readily lead to improved survival times due to the effects of competition between resistant and sensitive tumour cells. Very early palliation is also predicted to quickly yield near total tumour resistance and thus decrease survival duration. Finally, our simulations indicate that failed curative attempts using dose densification, a common protocol escalation strategy, can reduce survival times

Tips and tricks in triple-negative breast cancer: how to manage patients in real-life practice?

Journal ArticleSCOPUS: cp.jinfo:eu-repo/semantics/publishe

A fuzzy gene expression-based computational approach improves breast cancer prognostication

A fuzzy computational approach that takes into account several molecular subtypes in order to provide more accurate breast cancer prognosi

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

First-line chemotherapy for ovarian cancer – the controversy continues

British Journal of Cancer (2002) 87, 813–814. doi:10.1038/sj.bjc.6600568 www.bjcancer.co