Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer

Aim:to evaluate the activity and acute toxicity of thecombination of weekly paclitaxel as first-line chemotherapy andtrastuzumab, in patients with HER-2/neu overexpressing advanced breastcancer (ABC).Background:Weekly paclitaxel has beenshown to be a well tolerated treatment with considerable activity inpatients with ABC. Clinical trials with transtuzumab, a humanizedanti-p185 HER-2/neu monoclonal antibody have demonstrated that thisagent produces objective responses in patients with ABC.Patients and methods:From December 1998 to April 2000, 34patients with HER-2/neu overexpressing ABC were treated with weeklypaclitaxel; given by one-hour infusion at a dose of 90 mg/m²immediately followed by trastuzumab, 4 mg/kg as a loading dose and2 mg/kg i.v. given over 30 min, thereafter weekly for at least 12 weeks.Expression of HER-2/neu was determined by immunohistochemical analysison fixed, paraffin-embedded tissues. Eligible patients were required tohave 25% stained tumor cells.Results:Thirty-three patients completed at least 12 weeks of combinedtreatment. After completion of the 12th week of treatment, four patients(12%) achieved complete and 17 (50%) partial response.Median duration of response was 11.6 months. More frequent side effectsincluded anemia (56%), neutropenia (27%), peripheralneuropathy (78%), diarrhea (30%), alopecia (70%),arthralgias/myalgias (62%), fatigue (59%) andhypersensitivity reactions (62%). Median time to progression wasnine months while median survival had not been reachedConclusions:The combination of weekly paclitaxel andtrastuzumab is a safe and active regimen for patients with HER-2/neuoverexpressing ABC. Randomized phase III studies with this combinationare warranted.