Olivia Le Saux1,2,3,4, Aurélie Bourmaud5,6,7, Catherine Rioufol5,8,7,9, Olivier Colomban5,7, Jérôme Guitton5,7, Vérane Schwiertz8,9, Véronique Regnier5,6,7, Benoit You5,10,7,9, Florence Ranchon5,8,7,9, Raymonde Maraval-Gaget10,9, Pascal Girard5,7,11, Franck Chauvin5,6,7, Gilles Freyer5,10,7,9, Michel Tod5,7, Emilie Henin5,7, Véronique Trillet-Lenoir5,10,7,9. 1. EMR3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard, Oullins, France. olivia.le-saux@chu-lyon.fr. 2. Service d'Oncologie Médicale, Centre Hospitalo-Universitaire Lyon-Sud, Pierre-Bénite, France. olivia.le-saux@chu-lyon.fr. 3. Université de Lyon, Lyon, France. olivia.le-saux@chu-lyon.fr. 4. Hospices Civils de Lyon, Lyon, France. olivia.le-saux@chu-lyon.fr. 5. EMR3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard, Oullins, France. 6. Hygée center, Lucien Neuwirth Cancer institut, and CIC 14 08 INSERM, Saint Etienne, France. 7. Université de Lyon, Lyon, France. 8. Service pharmaceutique - Unité de pharmacie clinique oncologique, Centre Hospitalo-Universitaire Lyon-Sud, Pierre Bénite, France. 9. Hospices Civils de Lyon, Lyon, France. 10. Service d'Oncologie Médicale, Centre Hospitalo-Universitaire Lyon-Sud, Pierre-Bénite, France. 11. Merck Institute for Pharmacometrics, Merck Serono S.A., Switzerland, a Subsidiary of Merck KGaA, Darmstadt, Germany.
Abstract
PURPOSE: The aim of the OCTO clinical study was to measure patients' adherence to capecitabine-based treatment. METHODS: A cohort of ambulatory patients treated with capecitabine monotherapy for either locally advanced or metastatic, breast or colorectal cancer was monitored for 6 cycles. Adherence was assessed in all patients by self-completed questionnaires on disease, pill-count and pharmacological dosage of FBAL (metabolite of capecitabine); and in half of the cohort by electronic medication event monitoring systems (MEMS™) recording the opening times of the device. RESULTS: Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range 1-6). Hand-foot syndrome (HFS) was the most frequently reported toxicity (35% patients), and to a lesser extent fatigue and/or asthenia (21%), nausea and/or vomiting (13%) and diarrhea (11%). In the MEMS™ cohort, 20 patients were included. Patients' adherence was excellent with very few missing occasions (23/2272 records). Close analysis of MEMS™ data revealed unexpected medication patterns, such as patients taking extra days of medication beyond planned cycle, patients taking extra doses per day and patients missing a day of dosing and "compensating" by taking extra the following day (N = 7, 18%). A trend was found between over-adherence and high-grade toxicity (grades 3 and/or 4): OR 4.74 [0.65-45.2], p = 0.13 and higher AUC (p = 0.16). There was a trend towards increased AUC of FBAL in over-adherent patients (p = 0.16). CONCLUSION: Adherence to oral anticancer chemotherapy was found excellent in this population suggesting over-adherence to capecitabine and potential safety implications for outpatients' drugs.
PURPOSE: The aim of the OCTO clinical study was to measure patients' adherence to capecitabine-based treatment. METHODS: A cohort of ambulatory patients treated with capecitabine monotherapy for either locally advanced or metastatic, breast or colorectal cancer was monitored for 6 cycles. Adherence was assessed in all patients by self-completed questionnaires on disease, pill-count and pharmacological dosage of FBAL (metabolite of capecitabine); and in half of the cohort by electronic medication event monitoring systems (MEMS™) recording the opening times of the device. RESULTS: Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range 1-6). Hand-foot syndrome (HFS) was the most frequently reported toxicity (35% patients), and to a lesser extent fatigue and/or asthenia (21%), nausea and/or vomiting (13%) and diarrhea (11%). In the MEMS™ cohort, 20 patients were included. Patients' adherence was excellent with very few missing occasions (23/2272 records). Close analysis of MEMS™ data revealed unexpected medication patterns, such as patients taking extra days of medication beyond planned cycle, patients taking extra doses per day and patients missing a day of dosing and "compensating" by taking extra the following day (N = 7, 18%). A trend was found between over-adherence and high-grade toxicity (grades 3 and/or 4): OR 4.74 [0.65-45.2], p = 0.13 and higher AUC (p = 0.16). There was a trend towards increased AUC of FBAL in over-adherent patients (p = 0.16). CONCLUSION: Adherence to oral anticancer chemotherapy was found excellent in this population suggesting over-adherence to capecitabine and potential safety implications for outpatients' drugs.