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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.

Background. High-dose chemotheraphy with hematopoietic support produces high rates of response in metastic breast cancer. To facilitate new high-dose regimens there is a need to identify active agents with toxicity limited to hematopoietic suppression. Cisplatin/etoposide is a highly active regimen in metastatic breast cancer, but cisplatin dose-escalation is limited by nonhematologic toxicity. Carboplatin is active in breast cancer and has marrow-dominant toxicity. Demonstration of activity for the combination of carboplatin and etoposide would facilitate their inclusion in high-dose programs. Methods. A single treatment arm prospective Phase II study in patients with measurable or evaluable breast cancer was done. Results. Forty-six patients with metastic breast cancer were treated with the combination of carboplatin and etoposide. Among 19 patients without prior chemotherapy, one complete and seven partial responses were observed, for an objective response rate of 42% (95% exact confidence intervals [CI], 200-67%). One partial response was seen among 12 patients with prior chemotherapy limited to the adjuvant setting. No responses were seen among 14 patients who had received prior chemotherapy for metastic cancer. Two treatment-related deaths occurred, both attributable to sepsis. One patient returned to her community for treatment after receiving one course of protocol therapy before response assessment and could not be studied for response. Conclusion. The activity observed with this regimen in patients with no prior chemotheraphy coupled with its potential for dose escalation suggests a possible role in high-dose programs with hematopoietic support. The inactivity of the combination in patients with prior therapy for metastic breast cancer indicates that there is no advantage to its use in the salvage setting. Cancer 1993; 71:1254-7.

The authors report a case of suramin-induced immune-mediated thrombocytopenia occurring in a patient on a Phase II protocol for treatment of metastatic renal cell carcinoma. On withdrawal of suramin, the acute and severe thrombocytopenia did not respond initially to plasmapheresis; subsequently, it resolved promptly and dramatically during the administration of intravenous gamma globulin, also coinciding with a decline in suramin blood levels. Results of immunologic and coagulation studies are reported and clinical implications discussed. Cancer 1993; 71:851-4.

Tumors that develop in the lining of the urinary tract are often responsive to chemotherapy. Unfortunately, the responses of these urothelial tumors are generally not long-lasting, and long-term patient survival is infrequent. Observing that cisplatin, a compound including platinum in its chemical structure, is effective against urothelial tumors, researchers have begun to evaluate other metal compounds in the search for more effective chemotherapeutic drugs. One metal that has shown some promise is gallium. In the present study, researchers evaluated the use of gallium nitrate in the treatment of 40 patients with urothelial cancer. All patients had advanced cancer which had already proved unresponsive to a standard treatment of methotrexate, vinblastine, doxorubicin, and cisplatin. Gallium nitrate was administered by continuous infusion; in 17 patients, the dose was gradually escalated to determine the toxicity of the drug. The compound was found to be relatively well tolerated, but no clinical effectiveness was observed until a dose of 350 milligrams of gallium nitrate per square meter of body area per day was given. Twenty-three patients were started at this level with increments to 400 milligrams if no toxic effects were observed. Suppression of the bone marrow, a common complication of chemotherapy, was minimal among these patients, but 3 of the 11 patients who received 400 milligram (per square meter) daily doses of gallium nitrate developed abnormalities of the optic nerve. These abnormalities, which prevented the use of a higher dose, were fortunately reversible and resolved after chemotherapeutic treatment. Three partial responses and one complete response were observed in these patients. In a group of patients with advanced cancer who have already failed chemotherapy, this is a promising result and suggests that further evaluation of gallium nitrate in the treatment of urothelial tract cancer is appropriate. The four responses in the present group of patients lasted from two to eight months before disease progression continued. (Consumer Summary produced by Reliance Medical Information, Inc.)