Docetaxel Effective as First-Line Breast Cancer Therapy

SAN ANTONIO--First-line chemotherapy with docetaxel (Taxotere)produced response rates as high as 68% in a series of studiesinvolving patients with advanced, metastatic breast cancer.

Two evaluations of a 100 mg/m² dose of docetaxel resultedin identical 68% response rates in a total of 68 patients. Theresponse rate dropped to 52% in an evaluation of a 75 mg/m²dose, Dr. Pierre Kerbrat reported at the San Antonio Breast CancerSymposium.

The three studies were conducted by the European Organizationfor Research and Treatment in Cancer (EORTC) Clinical Study Group(CSG). Collectively, the studies enrolled 110 patients, 99 ofwhom were evaluable for responses.

All patients had measurable metas-tases, and about a third hadmetastatic involvement of at least two organs, said Dr. Kerbrat,a medical oncologist at the Eugene Marquis Center, Rennes, France.None of the patients had received primary chemotherapy, but morethan half had received prior adjuvant chemotherapy.

The first trial, CSG1, included 31 evaluable patients treatedwith the higher dose of docetaxel every 3 weeks; CSG3 evaluated37 patients who received the higher dose preceded by 1 day bypre-medication with corticosteroids and histamine antagonists.The second trial, CSG2, evaluated the lower docetaxel dose in31 patients. No patient in any of the three groups received growthfactors.

The 68% overall response rate in the 100 mg/m² groups includedfive complete responders in CSG1 and two in CSG3. Four patientshad complete responses in CSG2. Major responses were seen in 70%to 75% of patients with visceral and liver metastases in the high-dosestudies, compared with 52% and 44% in the 75 mg/m² group.

The median duration of response was 44 weeks in CSG1 and 34 weeksin CSG2. Median response duration has not been reached in CSG3but has ranged between 9 and 36 weeks, Dr. Kerbrat said.

Grade 4 neutropenia was the major hematologic toxicity in allthree studies. However, the condition was short-lived, generallyresolving in 7 days or less.

Fluid retention represented the major chronic toxicity, and wasjudged severe in 11% (CSG3) to 18% (CSG1) of patients. The incidenceof fluid retention observed in CSG1 led to the evaluation of thelower docetaxel dose in CSG2, Dr. Kerbrat said. However, the lowerdose had no appreciable effect on the condition, nor did the premedicationused in CSG3. He said that a planned fourth study will evaluatethe 100 mg/m² docetaxel dose preceded by 3 days of premedicationwith corticosteroids and the capillary protector diosmine.