Preventive dose reduction of capecitabine in elderly population

Background: Nowadays life expectancy is longer than a few decades ago and entails an increase in elderly population, defined as people over the age of 65. Since old age is a well known risk factor for developing neoplasia, in the future we can expect an increase in elderly cancer patients, a different population as far as the pharmacodynamic and pharmacokinetic processes are concerned. The objective of this retrospective, mono-institutional study is to compare the efficacy and tolerability of the oral drug capecitabine among patients over 75 years compared to the reported data in literature. Patients and methods: 117 pts older than 75 years treated with capecitabine as monotherapy (67% of patients) or in combination with other anti tumor drugs (33%) from 2006 to 2016 were evaluated. Colon, breast and stomach cancers were the most represented tumors (76%, 13% and 11% respectively); 58% were stage IV. All therapeutic regimens (adjuvant and advanced stage treatments) containing capecitabine were considered. A dose reduction of 25% of capecitabine was preventively applied at the beginning of the treatment. Results: In this series, the median age was 80 years, ECOG PS 0-1. The median number of comorbidities was 2,8. DCR, PFS and OS were evaluated and compared to randomized trials in literature. DCR in this study was much lower (48% vs. 67,2%), but PFS and OS were not different (PFS: 5 vs. 5,7 months. OS: 11 vs. 13 months). Adverse Drug Reactions (ADR) were evaluated to assess tolerability. 3% of our patients had hematological ADR (grade III) and 24% of them non-hematological ADR (including diarrhea, asthenia, mucositis of grade III). In literature ADR are much more frequently reported (13% of hematological and 43% of non-hematological ADR). Conclusions: Capecitabine is an oral anti tumor drug largely used in a variety of diffuse cancers (colon-rectum, stomach, breast). Elderly patients, with their physiologically altered metabolism processes, represent a current and future challenge in the treatment of a part of population increasing over time. In this study we found that a preventive 25% dose reduction of capecitabine reduces ADR, but at the same time it implies a reduction in efficacy. Further prospective studies are needed to understand if this reduced efficacy is due to physiological alterations peculiar of the elderly patients or to the numerous associated comorbidities, and if combination therapy is safer than monotherapy in this subset of patients.