Weekly administration of taxanes as palliative treatment in
metastatic breast cancer has been reported with significantly reduced
hematologic toxicity and comparable efficacy to standard every-3-week
protocols. This study update provides mature results with weekly
docetaxel (Taxotere) in a larger patient population.
Eligibility criteria for this study included measurable disease,
prior chemotherapy for metastatic disease, and ECOG (Eastern
Cooperative Oncology Group) performance status £ 2.
The protocol design consisted of docetaxel, 40 mg/m²/30 min
infusion weekly ´ 6, followed by a
2-week rest. Patients were premedicated with dexamethasone, 8 mg
intravenously before docetaxel administration, followed by oral
dexamethasone, 4 mg on the next day.
The patient characteristics were as follows: 41 evaluable patients;
ECOG performance status 0/1/2: 21/18/2 patients; median age: 55.2
years (range: 4771 years); all had one to three previous
chemotherapy protocols; prior epirubicin (Ellence): 25 (61%); prior
paclitaxel (Taxol): 6 (15%); delivered median dose intensity of
docetaxel: 36 mg/m²/week.
Toxicity included leukopenia (grade 2/3/4): 27%/10%/2% (maximum
tolerated dose, 45 mg/m²/week); no febrile neutropenia; nail
toxicity (1/2): 34%; edema (1): 8%; no grade 24 cumulative
sensory neuropathy; alopecia (2/3): 76%; asthenia (1/2): 17%;
conjunctivitis (2): 2%; delay of treatment by 1 week: 7%; dose
reduction to 35 mg/m²/week: 10%.
Response rates were as follows: complete response: 12%; partial
response: 36%; no change: 40%; progressive disease: 12%; 3 of 6
patients with prior weekly paclitaxel responded to weekly docetaxel.
Median duration of remission was 8.8 months (range: 212
months); median survival time was 12.8 months.
CONCLUSION: Weekly docetaxel has definite activity in
chemotherapy-pretreated breast cancer that is comparable to 100
mg/m² every 3 weeks, but with substantially reduced grade 3/4
leukocyte toxicity. The low incidence of leukopenia facilitates
combination therapy without compromise of docetaxel dosing. The
recommended weekly dose is 40 mg/m², as further dose escalation
results in grade 3/4 cumulative leukopenia, indicating a narrow
toxicity margin and a maximum tolerated dose between 40 and 45 mg/m².