The choice of adjuvant combination therapies with taxanes: rationale and issues addressed in ongoing studies

The taxanes are emerging as the most powerful compounds in breast cancer. Both compounds, paclitaxel and docetaxel, have been evaluated in the metastatic setting before proceeding with adjuvant trials. Docetaxel was shown in phase III trials to be superior, in particular, in terms of time to progression and survival, to salvage polychemotherapies after failure of prior chemotherapy including anthracyclines. Also, after failure of alkylating agents, a benefit in favor of docetaxel was reported when compared to doxorubicin, whereas paclitaxel was reported to be either as efficacious or inferior to doxorubicin, while being comparable to cyclophosphamide/methotrexate/5-fluorouracil. The role of taxanes in combination with anthracyclines in first-line therapy of advanced breast cancer is still unclear although emerging. One phase III trial showed the significant superiority of doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) in terms of response and time to progression. Several phase II studies with paclitaxel (over 3 hours) and anthracyclines in the metastatic setting showed high efficacy, but they also showed cardiac toxicity related to a pharmacokinetic interaction between the 2 agents. This fact led to the implementation of metastatic strategies (several phase III trials) aimed at avoiding the pharmacokinetic interaction or specifically limiting the cardiac toxicity that resulted in contradictory results. Consequently, adjuvant strategies with paclitaxel focused mostly 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. Results of all of these trials in the adjuvant setting are eagerly awaited in order to establish the role of taxanes in adjuvant breast cancer.