Comparison of weekly docetaxel regimens in prostate cancer: A systematic review and network analysis.

Abstract

e17104 Background: Docetaxel is one of the most widely used drugs for chemotherapy, both indicated for early onset and metastatic hormone-sensitive prostate cancer. While weekly regimen is widely used, certain studies have noted better safety profiles of biweekly and 3-weekly regimens, thus beneficial in patients with comorbidities. This systematic review and network meta-analysis aims to assess the efficacy of biweekly and triweekly regimens compared to the standard weekly docetaxel in terms of response, overall survival (OS), and incidence of adverse events. Methods: Literature search was conducted across five databases to identify cohorts or trials assessing the comparative efficacy of various weekly regimens of docetaxel. Dichotomous variables were quantified as risk ratios (RR) while continuous variables were assessed as hazard ratio (HR) and 95%CI. Analysis was performed using netmeta package of R employing a common-effects model. Results: Eleven studies comprising 1,664 patients (weekly=191, biweekly=576, triweekly=898) were included for further quantitative analysis. A common comparator of “once-weekly” regimen was chosen to assess the efficacy of biweekly and triweekly regimens. No difference was noted in OS, with biweekly (HR: 1.52; 95%CI: 0.87, 2.68; p=0.14) and triweekly (HR: 1.49; 95%CI: 0.86, 2.58; p=0.15) regimens associated with slightly higher but insignificant survival. Prostate-specific antigen (PSA) reduction rate was no different between all three regimens. Notably, risk of treatment failure was highest in triweekly (RR: 10.91; 95%CI: 6.94, 14.87; P<0.0001), followed by biweekly (RR: 8.49; 95%CI: 4.65, 12.33; p<0.0001) regimens, which could be accounted for due to the lesser cumulative dose. Incidence of any adverse event was insignificantly higher in once-weekly regimen. However, hematotoxicity was considerably higher in triweekly regimens (RR: 3.2; 95%CI: 1.49, 6.89; p=0.003), followed by biweekly regimens (RR: 3.70; 95%CI: 1.41, 9.73; p=0.008). The lowest overall hematological side effects were observed on the use of once-weekly docetaxel. Similarly, the risk of febrile neutropenia was significantly higher in triweekly docetaxel (RR: 12.31; 95%CI: 1.32, 114.50; p=0.03). The risk of anemia, neutropenia, arthralgia, and thrombocytopenia was similar across all regimens. Similarly, gastrointestinal adverse events like vomiting, nausea, diarrhea, and anorexia carried equal risk across all arms. Conclusions: While immediate response and overall survival were equal in all arms, triweekly and biweekly regimens were associated with a significantly higher risk of treatment failure. Despite being introduced to potentially cause lesser adverse events, triweekly and biweekly docetaxel increased the risk of hematotoxicity. Further trials are needed to assess the efficacy and safety of these weekly regimens.