CENTRAL-NERVOUS-SYSTEM PROGRESSION OF METASTATIC BREAST-CANCER IN PATIENTS TREATED WITH PACLITAXEL

Background. The possibility of tumor sanctuary sites in the central nervous system (CNS) of patients receiving paclitaxel has been suggested by laboratory data identifying low concentrations of drug in the brain and cerebrospinal fluid (CSF) of rats. Methods. The pattern of disease progression in patients with metastatic breast cancer who had an initial response to paclitaxel treatment in five Phase II trials at the Memorial Sloan-Kettering Cancer Center was reviewed. Results. Of 152 patients, 53 had a partial or complete response, and 25 had a minor response. Of the 78 patients who responded to paclitaxel, 52 had subsequent disease progression, 22 changed treatments before progression occurred (as specified by the protocol and/or to receive high dose consolidation chemotherapy), 2 stopped receiving treatment because of toxicity, 1 continued receiving treatment, and 1 died with no evidence of disease progression. Six of the 52 patients who progressed after initially responding to paclitaxel had isolated CNS progression while maintaining their systemic response (leptomeningeal metastasis in three, brain metastases in two, brain and leptomeningeal metastases in one). One patient had CNS progression (brain metastases) associated with other systemic sites of progression. All patients with CNS disease developed neurologic symptoms, prompting neurologic evaluation; one had only a mild headache, which was not recognized until evaluation for paclitaxel-related peripheral neuropathy. Conclusions. These data suggest that the CNS, and particularly the CSF, is an important sanctuary site for patients with metastatic breast cancer receiving paclitaxel.