The influence of docetaxel schedule on treatment tolerability and efficacy in patients with metastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background Administration of single-agent docetaxel in a weekly schedule may offer similar efficacy, with a more favorable toxicity profile, compared to a three-weekly schedule in patients with metastatic breast cancer. Methods The original search of Medline, Embase, and Scopus was performed in September 2018 and references were updated with additional searches up to January 2021. Two reviewers independently screened the identified literature based on a predefined set of criteria. Randomized controlled trials investigating the use of weekly versus three-weekly docetaxel in metastatic breast cancer patients were included. Results Four randomized controlled trials (N = 459 patients) were included in the final analyses. No significant differences were found in terms of objective response rate (risk ratio (RR) 0.75, 95% confidence interval (CI): 0.54 – 1.05), progression-free survival (hazard ratio (HR) 0.95, 95% CI: 0.71 – 1.26) or overall survival (HR 0.95, 95% CI: 0.70 – 1.29) between weekly and three-weekly docetaxel, respectively. Weekly docetaxel was associated with a significantly lower risk of grade 3/4 neutropenia (RR 0.16, 95% CI: 0.10 – 0.27), febrile neutropenia (RR 0.21, 95% CI: 0.08 – 0.55), and neuropathy (RR 0.29, 95% CI: 0.11 – 0.78). Although the risk of epiphora (≥ grade 3/leading to treatment withdrawal, RR 3.62, 95% CI: 1.07–12.22) and onycholysis (≥ grade 2/leading to treatment withdrawal, RR 3.90, 95% CI: 1.34 – 11.32) was increased. Conclusions Weekly docetaxel is associated with a lower risk of neutropenia, febrile neutropenia and neuropathy than the three-weekly docetaxel schedule in metastatic breast cancer patients. However, the risk of onycholysis, epiphora, and treatment discontinuation seems increased with weekly administration. No significant differences in efficacy outcomes were found. Weekly docetaxel might be an alternative for patients at risk for developing neutropenia.

Time above threshold plasma concentrations as pharmacokinetic parameter in the comparison of oral and intravenous docetaxel treatment of breast cancer tumors

“…Remarkably, relatively few cases of severe hematological toxicity were observed in Phase I studies with oral docetaxel compared with incidences reported with both i.v. docetaxel, where hematological toxicity is dose limiting [24,41,42]. Potentially, there is a discrepancy between the in vitro and in vivo sensitivity of myeloid and lymphoid cells which may be the result of differences in drug exposure due to the spatial organization of the bone marrow or of protective effects of other cells present in the bone marrow microenvironment [43].…”

“…Remarkably, relatively few cases of severe hematological toxicity were observed in Phase I studies with oral docetaxel compared with incidences reported with both i.v. docetaxel, where hematological toxicity is dose limiting [24,41,42].…”

“…In these schedules, doses of 30-40 mg/ m 2 are administered weekly and are associated with a significantly reduced risk of neutropenia compared to the 3-weekly i.v. schedules [41]. Although, other factors such as reduced dose intensity reported with weekly schedules may also contribute to this different toxicity profile [44].…”

Targeting Breast Cancer: An Overlook on Current Strategies

“…Adverse effects are represented by of neutropenia, febrile neutropenia, neuropathy, onycholysis, epiphora, and toxicity, often leading to treatment discontinuation. Moreover, docetaxel is a highly lipophilic drug with very poor water solubility and instability [ 170 ]. Cabazitaxel is a recent taxoid agent showing in vitro and in vivo activity against cell lines and tumors resistant to docetaxel and paclitaxel [ 171 ].…”

SBFI-26 enhances apoptosis in docetaxel-treated triple-negative breast cancer cells by increasing ROS levels

“…[11][12][13] Due to its therapeutic index, docetaxel, a microtubuletargeting agent, has garnered significant attention in cancer chemotherapy. 14 Docetaxel, a taxane oncology drug, exhibits cytotoxic potential and clinical efficacy against various malignancies, including breast, lung, and ovarian cancers. It induces tubulin monomer polymerization, inhibits depolymerization, and causes G2/M cell cycle arrest during mitosis, ultimately leading to cell death.…”