ROMEOptimizing premedication and use of growth factors
can improve the tolerability of docetaxel (Taxotere) while
maintaining the agents activity in patients with
anthracycline-resistant advanced breast cancer, according to results
of a small Italian study presented at the San Antonio Breast Cancer Symposium.
Pretreatment with dex-amethasone and ondanse-tron (Zofran) and
supportive use of lenograstim (G-CSF) were associated with a reduced
incidence of fluid retention and neutropenia, compared with patients
who received only prednisone pretreatment.
This study confirms the previously reported activity of
docetaxel in anthracycline-resistant breast cancer patients,
said Cecilia Nisticò, MD, an oncologist at the Regina Elena
Cancer Institute, Rome. Prophylactic G-CSF significantly
reduces the incidence of severe neutropenia, with or without fever,
and the need for dose reduction. Premedication with dexamethasone
appears to reduce the incidence of fluid retention syndrome.
Dr. Nisticò reported findings in 55 advanced breast cancer
patients, all of whom had a history of anthracycline therapy. Four
patients were anthracycline refractory, and 18 exhibited resistance
to anthracyclines. The median doxorubicin dose in the population was
300 mg/m2, and among those treated with epirubicin, the median dose
was 600 mg/m².
The population included 11 patients who had prior adjuvant
chemotherapy, 21 patients who had prior treatment for advanced
disease, and 23 patients who had received both adjuvant therapy and
treatment for advanced disease. Additionally, 22 patients had
received two or more lines of therapy for advanced disease.
Visceral metastases predominated in 34 patients, and 35 had two or
more metastatic sites. About half the patients had liver metastases.
All the patients received 100 mg/m² of docetaxel every 3 weeks
plus one of two premedication regimens. A group of 29 patients
received 50 mg of prednisone orally, starting 13 hours prior to
docetaxel infusion and continuing for 3 days afterward twice daily
for a total of 11 doses.
The remaining 26 patients received 8 mg of intramuscular
dexamethasone, beginning 12 hours before chemotherapy and continuing
for 48 hours afterward for a total of four days. The second group
also received 8 mg of ondansetron by IV infusion during chemotherapy,
and 150 µg/m² of G-CSF, starting 4 days after chemotherapy
and continuing every other day for 4 days.
Docetaxel resulted in an overall response rate of 50.9% (28 of 55
patients), including four complete responses and 24 partial
responses. The responses were evenly distributed between the groups
receiving dexamethasone/ondansetron/G-CSF and prednisone alone.
Additionally, 17 patients had disease stabilization.
Major responses occurred in 16 of 25 patients with liver metastases,
and in 10 of 21 patients classified as anthracycline resistant or refractory.
Median overall survival was 12.5 months in patients who had a major
response vs 9 months for patients who had stable or progressive
disease. Median duration of response was 7 months.
The type of premedication regimen had a substantial impact on the
incidence of severe toxicity, Dr. Nisticò said. Seven patients
in the prednisone group experienced moderate-to-severe fluid
retention vs one in the IM dexamethasone cohort.
Effect of G-CSF
Grade 3-4 neutropenia occurred during 71 of 137 cycles of therapy in
the prednisone-only cohort, compared with 4 of 114 cycles in the
patients who received prophylactic G-CSF. Febrile neutropenia
occurred during 12 cycles of chemotherapy in prednisone-only
patients, and in none of the G-CSF patients. A 25% dose reduction was
required in three patients (six cycles) due to complicated
neutropenia in the prednisone- only group, while no dose reductions
were necessary in the G-CSF patients.