Over-adherence to capecitabine: a potential safety issue in breast and colorectal cancer patients

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.