Mortality, leukemic risk, and cardiovascular toxicity of adjuvant anthracycline and taxane chemotherapy in breast cancer: a meta-analysis

Abstract

The contribution of adjuvant taxanes (T) in cardiovascular toxicity, leukemic risk, and non-cancer-related deaths is unknown when they are added to anthracycline (A)-based chemotherapy for breast cancer. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the risk of cardiovascular toxicity, leukemia, neurotoxicity, and non-breast cancer-related mortality associated with T added to adjuvant A in breast cancer. PubMed was searched to identify relevant studies. Eligible studies included prospective RCTs in which approved T in combination with A (A + T) were compared with A alone as adjuvant chemotherapy for breast cancer. Summary incidence rates, relative risks (RRs), and 95 % confidence intervals were calculated by means of fixed- or random-effects models. A total of 27,039 patients from 15 RCTs were included. Compared with A alone, A + T was associated with a statistically similar risk of toxicity. Compared with control arms, A + T schedules with less cumulative dose of anthracyclines than control arms were associated with lower severe cardiotoxicity (RR = 0.41, [95% CI 0.26-0.66], P = 0.0002), venous thromboembolic events (RR 0.45, [95% CI 0.26-0.79], P = 0.006), and leukemic risk (RR 0.39; [95%CI 0.18-0.87] P = 0.02), but with an increased risk of non-breast cancer-related mortality (RR = 1.79, [95% CI 1.06-3.04] P = 0.03). In particular, this risk of death is greater when >3 cycles of A precede T in sequential schedules (RR 2.24, [1.2-4.21] P = 0.01). This meta-analysis suggests that A + T-based adjuvant chemotherapy is as toxic as A alone with no significant difference in non-breast cancer-related mortality. However, sequential A + T schedules are associated with less toxicity, but a significant increase in non-breast cancer-related mortality compared with control arms with a greater dose of A.