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Metastatic Breast Cancer Responds to Docetaxel, Doxorubicin, Cytoxan

Metastatic Breast Cancer Responds to Docetaxel, Doxorubicin, Cytoxan

SAN ANTONIO—A taxane-containing combination therapy has led to major objective responses in 75% to 80% of patients with metastatic breast cancer. Overall, 35 of 48 evaluable patients responded to the combination of docetaxel (Taxotere), doxorubicin, and cyclophosphamide, said Jean-Marc Nabholtz, MD, senior medical oncologist at the University of Alberta, Edmonton, Canada.

In his poster presentation at the San Antonio Breast Cancer Symposium, Dr. Nabholtz said that high response rates were observed at all metastatic sites, including the liver, and that the combination was associated with minimal cardiotoxicity.

The Canadian study involved 54 patients who had not received previous treatment for metastatic breast cancer. Prior adjuvant chemotherapy with non-anthracycline regimens was permitted.

The protocol used in the trial began with doxorubicin at a dose of 75 mg/m2 infused as a bolus on day 1, followed by cyclophosphamide at a dose of 500 mg/m2. An hour after the doxorubicin infusion, docetaxel was given at a dose of 75 mg/m2 infused over 1 hour. The regimen was repeated every 3 weeks. Pre-medication with dexamethasone and ciprofloxacin was standard for all patients, but the protocol did not allow for prophylactic use of G-CSF.

The 35 clinical responses included three complete responses in patients treated with the combination. Among 42 patients with measurable disease, 33 had objective responses, Dr. Nabholtz said. High response rates were seen in the liver, lung, bone, and other metastatic sites (see table). Data on duration of response and time to progression are still being analyzed.

Adverse Effects

Grade 4 neutropenia occurred in every patient, and 28% developed febrile neutropenia. However, the investigators considered the hematologic toxicity manageable, he said. Grade 3-4 infection occurred in 4% of patients.

Cardiotoxicity occurred in 3 of 54 patients evaluable for toxicity, and the incidence was low regardless of cumulative doxorubicin dose.

Among 32 patients who received a cumulative doxorubicin dose of less than 360 mg/m2, one had an asymptomatic decrease in left ventricular ejection fraction (LVEF). However, that patient discontinued therapy after cycle 7, as LVEF had declined from 62% pretreatment to 42% at a cumulative doxorubicin dose of 309 mg/m2. No patient developed symptomatic congestive heart failure (CHF).

Of 22 patients who received 360 mg/m2 or more of doxorubicin, three had asymptomatic decreases in LVEF, and one developed CHF at a cumulative doxorubicin dose of 400 mg/m2.

With respect to other nonhematologic toxicity, no patient developed grade 4 toxicity of any type. A total of 10 patients had grade 3 toxicity (nausea in 5, diarrhea in 2, and stomatitis in 3).

“We can now say that the combination of docetaxel and doxorubicin does not induce an increase in cardiotoxicity,” Dr. Nabholtz said. “That is a very important observation because it opens the door to large treatment trials.”

In fact, he added, two randomized trials have already begun. One trial will compare the combination used in the current study with fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy in metastatic disease. The other trial will evaluate paclitaxel (Taxol), doxorubicin, and cyclophosphamide in the adjuvant setting in patients with node-positive breast cancer.

 
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