High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel

Background: Clinically overt central nervous system (CNS) involvement occur s in 10%-15% of patients with advanced breast cancer. Patients and methods: The International Breast Cancer Study Group (IBCSG) c onducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) a s first-line therapy in advanced breast cancer patients. The study was expa nded into a phase II at the recommended doses of E 90 mg/m(2) and D 75 mg/m (2) every three weeks. From July 1996 to May 1998, a total of 92 patients ( median age 50 years) entered the two studies. Results: Twenty-eight out of ninety-two patients treated with the combinati on of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35 %), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Med ian time for the development of CNS metastases from the start of chemothera py was 15 months (range 5-42), if excluding the 6 patients presenting CNS p rogression within 3 months from start of treatment. It is notable that 11 p atients (39%) had progression in the CNS only. Median survival from appeara nce of brain metastases in the whole group was only three months (range 1-2 2). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in who m the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). Conclusions: As anthracycline- and taxane-containing regimens are increasin gly used both in the metastatic and in the adjuvant setting, a careful moni toring of any neurological symptom is advisable. Our preliminary observatio n on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.