Phase II trial and pharmacokinetic evaluation of cytosine arabinoside for leptomeningeal metastases from breast cancer.
PURPOSE: To determine the efficacy and pharmacokinetics of intraventricular cytosine arabinoside (Ara-C) as front-line treatment for leptomeningeal metastases from breast cancer. METHODS: Ten patients newly diagnosed with leptomeningeal metastases (LMM) from breast cancer were treated with 100 mg intraventricular cytosine arabinoside (IVT Ara-C) via an Ommaya reservoir. Treatment was administered three times a week for 2 weeks, then once a week for 4 weeks, and then once every 6 weeks for four cycles to responding patients. Nine patients were evaluable clinically, and seven patients underwent testing to determine the pharmacokinetic profile of Ara-C in the cerebrospinal fluid (CSF). RESULTS: Two patients had partial responses lasting 9 and 40 weeks, respectively. Two other patients had stable disease. The median survival duration was 30 weeks (range: 5-58 weeks). Seven patients died from LMM. Acute toxic effects associated with IVT Ara-C included meningismus, nausea, vomiting, and myelosuppression. The median peak Ara-C level in CSF was 16.69+/-6.30 mM (SD). The half life for elimination was 1.45+/-0.61 h (SD) There was no drug accumulation between courses. Neuropsychological evaluations were completed in eight patients, six (75%) of whom had preexisting cognitive deficits. Their condition generally improved over the course of treatment until the LMM progressed. No neurotoxic side effects of IVT Ara-C were observed in the two patients who had normal baseline cognitive assessments. CONCLUSIONS: IVT Ara-C at this dose and schedule has minimal activity as initial treatment for LMM from breast cancer despite achievement of high peak levels of the drug in the cerebrospinal fluid. A liposomal Ara-C formulation is currently under investigation.[1]References
- Phase II trial and pharmacokinetic evaluation of cytosine arabinoside for leptomeningeal metastases from breast cancer. Esteva, F.J., Soh, L.T., Holmes, F.A., Plunkett, W., Meyers, C.A., Forman, A.D., Hortobagyi, G.N. Cancer Chemother. Pharmacol. (2000) [Pubmed]
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