PURPOSE:Docetaxel is highly active in the treatment of patients with breast cancer. The principal dose-limiting toxicities of the 3-weekly regimen are neutropenia and febrile neutropenia. In a previous phase I dose-escalation study with granulocyte colony-stimulating factor (G-CSF) support, the recommended dose was determined to be docetaxel 160 mg/m(2) 3-weekly. The objectives of this phase II study were to determine the response rate and toxicity of this dose and schedule, given as first-line in patients with advanced breast cancer. Mobilisation of peripheral blood stem cells (PBSCs) was also investigated. PATIENTS AND METHODS:Eligible women had metastatic breast cancer and were aged 18-75 years with ECOG performance status < or =2. Strict criteria for liver function were followed, and adjuvant chemotherapy must have been completed at least 6 months previously. Treatment was docetaxel 160 mg/m(2) over 60-90 min every 21 days with G-CSF 5 micro g/kg/day until neutrophil recovery, for up to six cycles. A 3-day corticosteroid prophylaxis was given. Bloods samples to determine PBSC levels [CD34+, granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythroid (BFU-E)] were taken on days 6, 8, 9 and 11 following docetaxel. RESULTS:Twenty-five women with median age 50 years (range 35-66) were included. Seventeen (68%) had previously received adjuvant chemotherapy. In total, 112 cycles were delivered (median four per patient), with dose reductions required in 12.5% of cycles. G-CSF was given for a median of 6 days. The median neutrophil nadir was 0.5 x 10(9)/l and occurred a median 5 days after treatment. The median duration of grade 3 or 4 neutropenia was 2 days (range 1-7). Grade 4 neutropenia occurred in 44% of patients, but there was only one episode of febrile neutropenia. Five patients were taken off study due to toxicities that included oedema, neurosensory toxicity and asthenia. Confirmed partial response was seen in nine patients (37.5%; 95% confidence interval 19% to 59%). CD34+ cells, GM-CFC and BFU-E levels peaked at day 8 following docetaxel administration. The median CD34+ cell peak was 6.5 x 10(4)/ml, with only 20% of patients <2 x 10(4)/ml, a level below which leukapheresis is not usually attempted. CONCLUSIONS:Docetaxel 160 mg/m(2) was delivered with G-CSF support with a very low rate of febrile neutropenia. Non-haematological toxicity was significant, causing five patients to go off study. Effective mobilisation of PBSCs was seen. The response rate of 37.5% was less than that obtained in first-line studies using standard-dose docetaxel 100 mg/m(2), suggesting that there is no additional benefit in dose escalation of this cytotoxic agent in breast cancer patients using this schedule.