A phase II trial of split, low-dose docetaxel and low-dose capecitabine: A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer

Background: Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine Phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. Patients and Methods: Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m² on days 1 and 8 in combination with capecitabine 750 mg/m² twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). Results: Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events. Conclusion: Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.