Taxane/Anthracycline Combinations: Setting a New Standard in Breast Cancer?

Abstract

Among the novel chemotherapeutic drugs introduced in the 1990s, the taxanes have emerged as the most powerful compounds in breast cancer. Both compounds, paclitaxel and docetaxel, have been evaluated in metastatic settings before adjuvant trials proceeded. Docetaxel was shown in several phase III trials to be superior, particularly in terms of survival, for salvaging polychemotherapies after failure of prior chemotherapy, including that with anthracyclines. A benefit of docetaxel was also reported when compared with doxorubicin after failure of alkylating agents. In phase III trials paclitaxel was reported to be as efficacious over 24 hours as doxorubicin 60 mg/m 2 , while paclitaxel was significantly inferior to doxorubicin 75 mg/m 2 over 3 hours and was close to CMF in another trial. The role of taxanes in combination with anthracyclines in first-line therapy of advanced breast cancer is emerging. Following several phase II studies, a phase III trial showed the significant superiority of docetaxel/doxorubicin (AT) versus doxorubicin/cyclophosphamide (AC) in terms of response and time to progression. In several phase II studies with paclitaxel (3 hours), anthracyclines in the metastatic setting showed high efficacy but produced cardiac toxicity related to a pharmacokinetic interaction between the two agents. This finding led to the implementation of metastatic strategies (phase III trials) aimed at avoiding the pharmacokinetic interaction, while the adjuvant strategies with paclitaxel focused primarily on the sequential approach (AC followed by paclitaxel). In contrast, adjuvant strategies with docetaxel/anthracycline-based programs were implemented following both sequential and combination approaches. The Oncologist 2001;6(suppl 3):5-12

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

“…The median TTP in patients who responded was 13 months (95% CI 12 -14) and the median OS was 29 months (95% CI 22 -35). Our findings are similar to those reported for the docetaxel arm in a phase III trial in which doxorubicin (50 mg m À2 ) and docetaxel (75 mg m À2 ) was compared with doxorubicin (60 mg m À2 ) and cyclophosphamide (600 mg m À2 ) for a maximum of eight cycles in 423 patients with MBC (Nabholtz and Riva, 2001). Patients included in the docetaxel arm showed a significantly improved ORR (60%, P ¼ 0.012) and median TTP (37.1 weeks, P ¼ 0.0153).…”

Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study

“…However, for patients with early-stage disease for whom a cure is still possible, cardiotoxicity is less acceptable. Thus, more tolerable agents such as epidoxorubicin are likely to be combined with docetaxel in these patients (Bellot et al 1998, Gennari et al 1999, Mencel et al 2000, Nabholtz and Riva 2001, Reichman et al 1993. Unexpectedly, the combination of trastuzumab and anthracycline-containing regimens is associated with a significant incidence of cardiac dysfunction.…”

The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment – Current and Future Tools

“…Anthracycline plus taxane combinations yield the highest response rates achievable with conventional chemotherapy in the treatment of breast cancer [36]. This combination regimen has a rate of FN well above 20% and therefore makes the use of prophylactic G-CSF support necessary.…”