Combination Docetaxel/ Cyclophosphamide in Patients with Advanced Solid Tumors

Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as monotherapy in a number of tumors, including metastatic breast cancer. Therefore, we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors. A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel, both administered as 1-hour intravenous infusions once every 3 weeks. The dose levels of cyclophosphamide/ docetaxel were 600/60 mg/m² (group 0), 600/75 mg/m² (group 1), 700/75 mg/m² (group 2), 800/75 mg/m² (group 3), 800/85 mg/m² (group 4), 800/75 mg/m² (group 5), and 800/85 mg/m² (group 6). Patients with dose-limiting neutropenia in groups 5 and 6 received 300 μg of granulocyte colony-stimulating factor (G-CSF) (filgrastim [Neupogen]) support on days 2 through 9 during subsequent cycles of chemotherapy. All patients received premedication with 8 mg of dexamethasone twice daily for 5 days, beginning 1 day prior to chemotherapy. The dose-limiting toxicity was neutropenic fever. The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m² in previously treated patients and 800/75 mg/m² in previously untreated patients. G-CSF support did not allow for further dose escalation. Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69% in 32 patients with metastatic breast cancer (including 3 patients who achieved complete responses).