Docetaxel and Vinorelbine With Concurrent G-CSF Support: A Phase II Study in Stage IV Breast Cancer

Docetaxel (Taxotere) and vinorelbine (Navelbine) are active agents in the treatment of metastatic breast cancer. Preclinical data suggest that there may be synergism between vinca alkaloids and taxane compounds. The current study evaluates the combination of docetaxel and vinorelbine with concurrent granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) in anthracycline-refractory breast cancer. The objectives of this study are to determine the response rate, time to progression, survival, and toxicities of this regimen.

Eligibility includes stage IV breast cancer patients whose tumors relapsed or progressed while receiving, or within 12 months of receiving, an anthracycline, or who had received > 360 mg/m² doxorubicin. Prior paclitaxel (Taxol) treatment is permitted. Docetaxel is given at 60 mg/m² IV on day 1 of a 21-day cycle with dexamethasone premedication. Vinorelbine is given at a dose of 27.5 mg/m² IV on days 8 and 15. The G-CSF dose is 5 µg/kg/d subcutaneously, days 2–21 of each cycle.

Thirty-six patients are enrolled to date, with 32 evaluable for response. The median number of disease sites is 2; 84% of patients have visceral disease. The median number of prior treatment regimens is 1.8. Forty-five percent of patients have received prior paclitaxel. The median number of weeks on treatment is 15.3. The mean delivered dose intensity (DDI) of docetaxel is 19.8 mg/m²/wk. The mean DDI of vinorelbine is 17 mg/m²/wk. Thirty-one percent received concurrent trastuzumab (Herceptin).

Overall response is 59% (19 of 32 patients), with 31% complete responses (10 of 32 patients). Median time to progression, with 11.7 months median follow-up, is 10 months. Median survival has not yet been achieved. Of the 32 patients, 6 (18%) experienced grade 3/4 neutropenia, with 3 (9%) admitted for febrile neutropenia. Four patients (12%) were treated for infection. One death occurred due to gram-negative sepsis in a patient who was noncompliant with G-CSF. Four of 32 (12%) patients had grade 3 anemia. There was one case each of grade 3/4 diarrhea and stomatitis.

CONCLUSION: The combination of docetaxel and vinorelbine with concurrent G-CSF support appears to be well-tolerated when delivered at the doses and schedule in our protocol, and shows promising activity in the treatment of anthracycline-resistant metastatic breast cancer.

Click here for Dr. Gabriel N. Hortobagyi’s commentary on this abstract.