Background:Clinically overt central nervous system (CNS)involvement occurs in 10%–15% of patients with advancedbreast cancer.
Patients and methods:The International Breast Cancer Study Group(IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel(D) as first-line therapy in advanced breast cancer patients. The study wasexpanded into a phase II at the recommended doses of E 90 mg/m2 andD 75 mg/m2 every three weeks. From July 1996 to May 1998, a totalof 92 patients (median age 50 years) entered the two studies.
Results:Twenty-eight out of ninety-two patients treated with thecombination of E and D (30%) developed CNS metastases (95%confidence limits, 26%-35%), which were cerebral in twenty-fivepatients, leptomeningeal in two, and both in one. Of these 28 patients, 19(68%) had an objective response. Median time for the development of CNSmetastases from the start of chemotherapy was 15 months (range 5–42),if excluding the 6 patients presenting CNS progression within 3 months fromstart of treatment. It is notable that 11 patients (39%) hadprogression in the CNS only. Median survival from appearance of brainmetastases in the whole group was only three months (range 1–22).C-erbB-2 overexpression was found in 14 out of 16 patients (87%) inwhom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases).
Conclusions:As anthracycline- and taxane-containing regimens areincreasingly used both in the metastatic and in the adjuvant setting, acareful monitoring of any neurological symptom is advisable. Our preliminaryobservation on the possible increase of incidence of CNS involvement inpatients with advanced breast cancer receiving this effective drug combinationrequires further evaluation.