Optimizing Docetaxel Tolerability in Anthracycline-Resistant Breast Cancer

ROME—Optimizing premedication and use of growth factors can improve the tolerability of docetaxel (Taxotere) while maintaining the agent’s 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.”

The Patients

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.