A comparison of toxicity profiles between the lower and standard dose capecitabine in breast cancer: a systematic review and meta-analysis

Abstract

Purpose Capecitabine 1,000 mg/m2 bid × 14 days every 21 days (14/21) has been reported to have similar efficacy but more favorable toxicity profile than the approved dosage of 1,250 mg/m2. However, a dose-toxicity relationship of capecitabine in breast cancer patients has not been fully elucidated. We performed a systematic review and meta-analysis to compare a safety profile between capecitabine starting dose of 1,000 and 1,250 mg/m2 bid. Methods Studies were identified using PubMed, ASCO and San Antonio Breast Cancer Symposium abstract databases through December 2015. Eligible trials included phase II/ III trials of capecitabine monotherapy at 1,000 or 1,250 mg/m2 bid (14/21) for breast cancer patients that reported adequate safety data for all (Grade 1-4) or high (Grade 3-4) grade hand foot syndrome (HFS), diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, thrombocytopenia, or anemia, as well as dose reductions, treatment discontinuation or treatment-related deaths. The summary incidence was calculated using random- effects models. Results A total of 4,833 patients from 34 trials were included. 1,218 and 3,615 patients were treated with capecitabine 1,000 and 1,250 mg/m2 bid, respectively. A significantly lower incidence of dose reduction (15.9 vs. 39.0%; P = 0.007), high-grade HFS (12.0 vs. 19.0%; P = 0.01), diarrhea (5.3 vs. 9.1%; P = 0.01), and neutropenia (1.8 vs. 7.3%; P < 0.01) and all-grade neutropenia (5.8 vs. 25.4%; P = 0.01) was seen in capecitabine 1,000 mg/m2 compared to 1,250 mg/m2. Conclusions Capecitabine monotherapy at 1,000 mg/m2 bid (14/21) has a clinically meaningful and significantly better toxicity profile compared to 1,250 mg/m2 bid (14/21).

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

“…The pooled grade 3/4 AEs rate of 29.5% (95% CI 21.1–39.5) seemed to be a little high; this may be attributed to our taking into account the different kinds of observed AEs. Similar to the findings of our study, results from a recently published meta-analysis also show a better toxicity profile with the use of a lower dosage of capecitabine [ 47 ]. Most of the of MBC patients in this study were either pretreated or had chemotherapy resistance; these findings plus the OS data are optimistic and are further supported by the results of a recent, randomized, phase II study (NCT0141771) aimed to prove that MCT was effective and less toxic in comparison to standard chemotherapy [ 48 ].…”

Relationship of fatigue with cognitive performance in women with early‐stage breast cancer over 2 years

“…This suggests that fatigue is quite common and other clinical factors, including the neurophysiological effects of the breast cancer itself, likely contribute to the experience of fatigue rather than the effects of chemotherapy alone. We found that an increase in fatigue was reported during the chemotherapy treatment period, which supported the study hypotheses and was consistent with prior reports of fatigue in the context of chemotherapy . A decrease in fatigue severity, which occurred for most women by 1‐year post‐chemotherapy indicates that chemotherapy did not produce long‐term exacerbation of fatigue beyond the levels experienced prior to chemotherapy.…”

Older cancer patients and COVID‐19 outbreak: Practical considerations and recommendations

“…36 In this scenario, oral therapies limit the number of ambulatory visits thus reducing the nosocomial risk which is mostly related to hospital access, and can frequently be proposed as good alternatives to intravenous treatments, with evidence suggesting that low-dose or metronomic schedules may be as effective as standard scheduling, with lesser side effects. 37,38 Therefore, whenever available oral therapy should be preferred over intravenous therapy, and telephone and/or web-based contact should be planned to follow the course of therapy.…”