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Combining anthracycline and taxane for early-stage operable breast cancer was more effective than either anthracycline or taxane chemotherapy alone in reducing breast cancer recurrence and death, according to a meta-analysis.

Moreover, regimens with higher cumulative doses of anthracycline plus taxane were associated with the greatest benefit, according to a report from Jeremy Braybrooke, BM, PhD, of University Hospitals Bristol in England, and colleagues of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG).

"The large number of available trials makes this the first study to reliably show that anthracycline and taxane significantly reduces breast cancer recurrence and mortality compared with taxane regimens without anthracycline," the authors observed in .

"The finding that regimens with higher cumulative doses of anthracycline and taxane provide the greatest benefits ... challenges the current trend in clinical practice towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel-cyclophosphamide," they added.

Specifically, the researchers found that among trials of taxane regimens with or without anthracycline involving about 18,000 women, recurrence rates were about 14% lower (RR 0.86, 95% CI 0.79-0.93) with taxane regimens including anthracycline than without anthracycline. This translated into an absolute reduction of 2.6% (95% CI 0.9-4.2) in 10-year recurrence risk, while 10-year breast cancer mortality was reduced by 1.6% (95% CI 0.1-3.1).

Furthermore, they found that the most definitive reductions in recurrence were seen when anthracycline was added concurrently to docetaxel plus cyclophosphamide, versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12.3% vs 21.0%, RR 0.58, 95% CI 0.47-0.73). Meanwhile, there was no significant reduction in recurrence risk with sequential anthracycline plus taxane versus docetaxel plus cyclophosphamide (RR 0.94, 95% CI 0.83-1.06, P=0.30), suggesting that higher cumulative anthracycline and taxane doses in concurrent regimens were more efficacious.

"For women with operable breast cancer at high enough risk of recurrence to be offered chemotherapy, our study shows that using both an anthracycline and a taxane, achieves the best results," Braybrooke said in a release. "This important finding should be considered in clinical practice as there has been a recent shift towards using shorter chemotherapy regimens that include a taxane but not an anthracycline; our research demonstrates that this is less effective than combination treatment."

Braybrooke and his colleagues noted that concerns about the short-term and long-term side effects of anthracyclines has led to increased use of taxane chemotherapy without an anthracycline.

"Long-term dose-dependent risks of acute myeloid leukemia (AML) and heart failure with anthracyclines are well established," they wrote, adding that the benefits of chemotherapy need to outweigh the short- and long-term risk associated with treatment.

Here, they found no significant difference between treatment groups for death without recurrence, including from cardiovascular disease or other primary cancers, as well as no difference in the overall incidence of new, non-breast primary cancers with and without anthracycline. There was an increase in the incidence of AML with anthracycline, with one additional case per 700 women treated. However, the authors wrote, this "is fewer than previous reports suggest."

The findings from this meta-analysis are "clinically important," wrote Song-Jie Shen, MD, of the Peking Union Medical College, and Chang-Mei Liu, PhD, of the University of Chinese Academy of Sciences, both in Beijing, in a . "For patients at sufficient risk of recurrence, and fit enough to be offered chemotherapy, the combination of taxane and anthracycline can be suggested to achieve the best possible reductions in breast cancer recurrence and mortality."

Yet one chemotherapy regimen doesn't fit all breast cancer subtypes, they cautioned. "In particular, with the escalation of anti-HER2 therapy, prospective studies will be warranted to validate the more-the-better rule in chemotherapy within this setting."

For the present meta-analysis, the authors identified 28 trials comparing taxane-based regimens with and without anthracycline, 15 of which provided data on 18,103 women. In these 15 trials, the mean age of participants was 53 years, and 53% had cancers with lymph node involvement, 67% had estrogen receptor-positive tumors, 14% had HER2-positive tumors. Median follow-up was 5.4 years.

Separately, in an updated EBCTCG meta-analysis, 35 eligible trials assessing anthracycline-based regimens with and without taxanes provided patient-level data on 52,976 women.

These trials demonstrated a 13% average reduction in recurrence in anthracycline regimens with taxane compared with those without (RR 0.87, 95% CI 0.82-0.93), translating to an absolute reduction of 3.3% (95% CI 1.3-5.3) in 10-year risk of recurrence, and an absolute reduction in 10-year breast cancer mortality of 3.6% (95% CI 1.8-5.4).

Trials directly comparing anthracycline and taxane regimens "showed that a higher cumulative dose and more dose-intense schedules were more efficacious," the EBCTCG group reported.

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