Docetaxel, a taxane chemotherapeutic agent, is the mainstay of treatment for patients with MBC. It can be combined with capecitabine in patients who have failed first-line anthracycline therapy, with human epidermal growth factor receptor 2 (HER2)–targeted therapy for patients whose disease expresses that receptor type and as monotherapy in palliative care. However, its use is limited by life-threatening myelosuppression. Evidence is available that indicates that the frequency and extent of adverse events (AEs) associated with docetaxel may be mediated by both the dose and length of treatment.

Investigators conducted a systematic review and meta-analysis via a search of Medline (Ovid), Embase (Ovid), and Scopus databases through January 2021 to systematically identify and analyze efficacy and toxicity data from a randomized clinical trial that compared weekly versus 3-weekly single-agent docetaxel in patients with MBC. Nonrandomized prospective clinical trials, studies that did not directly compare weekly versus 3-weekly single-agent docetaxel schedules, those involving non-MBC patients, those that used docetaxel as adjuvant or neoadjuvant treatment, studies that did not report efficacy or toxicity outcomes, preclinical trials, review articles, letters, case reports, and conference abstracts that lacked sufficient information were excluded from analysis.

Four studies involving 459 patients were included in the meta-analysis. Of these 459 patients, 227 had received weekly docetaxel and 232 were administered docetaxel every 3 weeks.

Despite differences in study methodologies and the presence of bias due to missing data or selection bias, the researchers were able to assess hematological toxicity, nonhematological toxicity, treatment withdrawals, and efficacy.

For hematological toxicities, the pooled risk ratios found that weekly docetaxel was associated with an 84% lower relative risk of greater than grade 3 neutropenia (relative risk [RR] 0.16, 95% CI: 0.10-0.27, P <.001) and a 79% reduced risk of febrile neutropenia (RR 0.21, 95% CI: 0.08-0.55, P <.01) compared with the three-weekly regimen.

For nonhematological toxicities, while docetaxel was associated with a 71% reduced risk of neuropathy (RR 0.29, 95% CI: 0.11-0.78, P = .01), it was associated with a 3.62-fold higher risk of epiphora or lacrimation (RR 3.62, 95% CI: 1.07-12.22, P = .04) and a 3.9-fold greater risk of onycholysis (RR 3.9, 95% CI: 1.34-11.32, P = .01) that were associated with treatment withdrawal. Rate of treatment discontinuation was only reported in two of the four trials. However, when a meta-analysis was conducted of the risk of treatment discontinuations associated with these AEs, it reached borderline significance (RR 1.52, 95% CI: 1.00-2.32, P = .05)

There were no significant differences in efficacy between weekly versus every 3-week regimens of docetaxel in objective response rate (RR 0.75, 95% CI: 0.54-1.05, P = .09), progression-free survival (hazard ratio [HR] 0.95, 95% CI: 0.71-1.29, P = .75), and overall survival (HR = 1.05, 95% CI: 0.71-1.29, P = .75).

This study helps pharmacists treating patients with MBC distinguish between the benefits (i.e., decrease in neutropenia, febrile neutropenia, and neuropathy) and the risks (i.e., increased onycholysis, epiphora, and treatment discontinuation) associated with weekly versus 3-weekly docetaxel regimens, respectively.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to Breast Cancer Update.