A Cochrane review [Abstract] 1 included 33 studies with a total of 5284 subjects. Antitumour antibiotics are a class of cytotoxic agents including the anthracyclines (eg. doxorubicin and epirubicin); anthracenediones (mitoxantrone/mitozantrone); and mitomycin-C.
There was no statistically significant difference in survival between regimens that contained antitumour antibiotics and those that did not (HR 0.97, 95% CI 0.91-1.03, p = 0.35). Antitumour antibiotic regimens were favourably associated with time-to-progression (HR 0.84, 95% CI 0.77-0.91) and tumour response rates (odds ratio (OR) 1.34, 95% CI 1.21-1.48) although statistically significant heterogeneity was observed for these outcomes. Patients receiving anthracycline-containing regimens were more likely to experience toxic events compared to patients receiving non-antitumour antibiotic regimens.
A meta-analysis included 148 comparisons pertaining to 128 trials (26 031 patients, 22 different types of treatment). Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22% to 33% relative risk reductions in mortality (HR for standard-dose anthracycline-based combination: 0.67, 95% credibility interval 0.57 to 0.78). Several newer regimens achieved further benefits (eg, HR 0.67. 95% credibility interval 0.55 to 0.81 for single-drug taxane, 0.64, 95% credibility interval 0.53 to 0.78 for combination of anthracyclines with taxane, 0.49, 95% credibility interval 0.37 to 0.67 for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments.
A secondary analysis of the TRAIN-2 randomized, phase 3 trial 3 evaluated 3-year event-free survival (EFS) and overall survival (OS) of an anthracycline-free and anthracycline-containing regimen with dual ERBB2 (formerly HER2) blockade in patients with stage II and III ERBB2-positive breast cancer included 438 patients. A total of 23 EFS events (10.5%) occurred in the anthracycline group (n=219) and 21 EFS events (9.6%) occurred in the nonanthracycline group (n=219) (HR 0.90; 95% CI, 0.50 to 1.63; favoring nonanthracyclines). Three-year EFS estimates were 92.7% (95% CI, 89.3% to 96.2%) in the anthracycline group and 93.6% (95% CI, 90.4% to 96.9%) in the nonanthracycline group and 3-year OS estimates were 97.7% (95% CI, 95.7% to 99.7%) in the anthracycline group and 98.2% (95% CI, 96.4% to 100%) in the nonanthracycline group. The results were irrespective of hormone receptor and nodal status.
Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies).
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