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 221 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