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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. Cancer 1995; 76:232--6. Key words: paclitaxel, breast cancer, brain metastases, leptomeningeal metastasis.

Neurological complications are well recognized with alcohol abuse, and an increasing amount of literature is emerging describing neurological disease as a complication of other drugs of addiction (recreational drugs). This review covers recent papers related to alcohol and drug abuse.

Chemotherapy plus radiation therapy (RT) for primary CNS lymphoma (PCNSL) has significantly improved patient survival over RT alone, but there are late neurologic sequelae of RT, particularly in the elderly.We treated 13 patients over age 50 years (mean age 74 years) with chemotherapy alone as initial treatment for PCNSL. All received methotrexate (MTX) and procarbazine; in addition, five received thiotepa, four vincristine, and four vincristine and cytarabine. Ten achieved a complete response (CR), 2 a partial response (PR), and 1 progressed through treatment. Two patients with ocular lymphoma responded to MTX, procarbazine, and vincristine. Four of six patients who relapsed after achieving a CR or PR were treated with additional chemotherapy or RT, three achieved a CR and one a PR. Five patients remain in CR at 7.5 to 30 months, one is alive at 35 months but with progressive disease, six died of PCNSL at 5 to 30.5 months, and one died in CR of sulfur allergy 2 months after diagnosis. The Karnofsky Performance Status improved in 11 of 13 patients with treatment. Cognitive deficits were present in nine patients at diagnosis and improved in eight of these nine after chemotherapy. Only one patient developed new cognitive deficits, due to progressive tumor and possibly MTX leukoencephalopathy. Chemotherapy alone for PCNSL is effective in the elderly and eliminates the risk of RT-related neurotoxicity. RT can salvage those who relapse after chemotherapy.