Evaluation of patient-reported severity of hand-foot syndrome under capecitabine using a Markov modeling approach.

PURPOSE: The inclusion of the patient's perspective has become increasingly important when reporting adverse events and may assist in management of toxicity. The relationship between drug exposure and toxicity can be quantified by combining Markov elements with pharmacometric models. A minimal continuous-time Markov model (mCTMM) was applied to patient-reported outcomes using hand-foot syndrome (HFS) induced by capecitabine anti-cancer therapy as an example. METHODS: Patient-reported HFS grades over time of 150 patients from two observational studies treated with oral capecitabine were analyzed using a mCTMM approach. Grading of HFS severity was based on the Common Terminology Criteria for Adverse Events. The model was evaluated by visual predictive checks (VPC). Furthermore, a simulation study of the probability of HFS severity over time was performed in which the standard dosing regimen and dose adjustments according to HFS severity were investigated. RESULTS: The VPC of the developed dose-toxicity model indicated an accurate description of HFS severity over time. Individual absolute daily dose was found to be a predictor for HFS. The simulation study demonstrated a reduction of severe HFS using the recommended dose adjustment strategy. CONCLUSION: A minimal continuous-time Markov model was developed based on patient-reported severity of hand-foot syndrome under capecitabine. Thus, a modeling framework for patient-reported outcomes was created which may assist in the optimization of dosage regimens and adjustment strategies aiming at minimizing symptom burden during anti-cancer drug therapy.

Adherence management for patients with cancer taking capecitabine: a prospective two-arm cohort study.

OBJECTIVE: To develop and evaluate a multiprofessional modular medication management to assure adherence to capecitabine. METHODS: The study was conducted as a prospective, multicentred observational cohort study. All participants received pharmaceutical care consisting of oral and written information. Daily adherence was defined as percentage of days with correctly administered capecitabine doses and assessed using medication event monitoring. According to their daily adherence during the first cycle, patients were identified as initially non-adherent (<90% adherence) or adherent (≥90% adherence). Initially non-adherent patients received additional adherence support. RESULTS: Seventy-three patients with various tumour entities were enrolled, 58 were initially adherent and 15 non-adherent. Median daily adherence of initially non-adherent patients increased from 85.7% to 97.6% during the observation period of six cycles. Throughout all cycles, median daily adherence of initially adherent patients was 100.0%. Daily adherence was not associated with sociodemographic and disease-related factors. No patient was non-persistent. CONCLUSIONS: An early adherence screening effectively distinguishes between patients adhering and non-adhering to capecitabine. The provision of specific adherence support is associated with enhanced adherence of initially non-adherent patients, whereas initially adherent patients remain adherent for at least six cycles without specific support. Our needs-based approach helps to use available resources for adherence management efficiently.

Task allocation in cancer medication management - integrating the pharmacist.

OBJECTIVE: This study was conducted to define the task allocation in multiprofessional cancer medication management (MCMM) with a special focus on the role of the pharmacist as well as patient education and counseling. The acceptance of the proposed task allocation and the perceptions on multiprofessional teamwork were explored on a national level. METHODS: We held local focus group meetings (University of Bonn with collaboration partners) to identify MCMM tasks. With the Delphi technique the tasks were allocated to physicians, pharmacists and nurses. Professionals (members of the German Cancer Society) were approached nationwide via an online questionnaire to evaluate the acceptance of the MCMM model and explore their perceptions on multiprofessional teamwork. RESULTS: The MCMM model comprised 38 tasks including 11 on patient education and counseling. It was rated to be reasonable (79%) and feasible (68%). Barriers and benefits of multiprofessional teamwork stated were patient-, team-, therapy-, structure-, and resources-related. CONCLUSIONS: The MCMM model integrates the pharmacist with responsibilities in patient education and counseling as well as prevention of drug-related problems. The approach was generally appreciated nationwide by the professions. PRACTICE IMPLICATIONS: The proposed model can serve as a tool to trigger changes in cancer medication management.