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Evidence summaries

Antitumour Antibiotic Containing Regimens for Metastatic Breast Cancer

Chemotherapeutic regimens containing antitumour antibiotics appear to provide significant advantage for tumour response, time to progression, and mortality in women with metastatic breast cancer compared with nonanthracycline drugs. Level of evidence: "B"

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.

Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies).

    References

    • Lord S, Ghersi D, Gattellari M, Wortley S, Wilcken N, Simes J. Antitumour antibiotic containing regimens for metastatic breast cancer. Cochrane Database Syst Rev 2004 Oct 18;(4):CD003367. [PubMed]
    • Mauri D, Polyzos NP, Salanti G et al. Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer. J Natl Cancer Inst 2008;100(24):1780-91. [PubMed]

Primary/Secondary Keywords