Prospects with docetaxel in the treatment of patients with breast cancer

Docetaxel (Taxotere) has been shown to be one of the most active cytotoxic agents in patients with breast cancer, achieving response rates of 41% when used as second-line treatment for metastatic breast cancer (34% in anthracycline-refractory patients) and 50-72% when used as first-line therapy. In both situations meaningful response durations of 7-8 months have been obtained. Based on these results, docetaxel is a promising candidate for new therapeutic strategies in patients with breast cancer. Studies comparing docetaxel with paclitaxel or anthracyclines in first-line therapy are ongoing. These studies should allow for an unequivocal definition of activity of docetaxel, yet not alter--as such--therapeutic strategies. A number of regimens are currently being explored combining docetaxel with anthracyclines, vinorelbine, 5-fluorouracil, cyclophosphamide and cisplatin. The preliminary conclusions are as follows: the main side-effect is non-cumulative neutropenia of short duration, and response rates are > 75%. Further, no cumulative cardiotoxicity has been observed with doxorubicin. The duration of response and length of the progression-free survival cannot yet be defined. Another option for combination chemotherapy is sequential combinations, the value of which has been demonstrated in advanced breast cancer as well as in the adjuvant setting. The short duration and non-cumulative character of docetaxel-induced neutropenia are good rationales for the use of dose-densified docetaxel-containing regimens. A dose of 100 mg/m2/14 days can be used as single-agent therapy. A phase I trial combining cyclophosphamide at doses increased from 750 to 1200 mg/m2 and docetaxel at doses increased from 66 to 100 mg/m2 every 2 weeks, is ongoing; at the first dose-levels, the combination appears feasible although cumulative asthenia has been observed. Further, responses have been observed at all dose levels. The value of single-agent chemotherapy added to tamoxifen has been emphasised for stage I-II breast cancer in postmenopausal patients. A randomised phase III study comparing tamoxifen (20 mg/day for 5 years) and epirubicin (50 mg/m2 days 1 and 8/28 days for 6 cycles) with the same regimen with epirubicin for 3 months followed by docetaxel (100 mg/m2/21 days x 3) was initiated at the end of 1996. Thus, docetaxel is currently under study in most therapeutic situations to better define its impact on the prognosis and curability of patients with breast cancer.