) SarCNU (2-chloroethyl-3-sarcosinamide-1-nitrosourea, N5C364432) is a novel chloroethylnitrosourea which demonstrates selective cytotoxicity against primary human gliomas in vitro in the human tumor cloning assay and in vivo efficacy against human glioma xenografts as compared to BCNU, the standard CNU utilized in the treatment of gliomas. The selective cytotoxicity of SarCNU in the human glioma cell line, SKMG-l, is associated with increased intracellular drug accumulation~secondary to transport via the extraneuronal catecholamine uptake2 carrier. SarCNU is representative of a potentially new class of anticancer agents that displays increased antitumor activity by exploiting a physiological aspect of the tumor cell. This study will evaluate the toxicity and pharmacokinetics of SarCNU when given as a 1 hour infusion on days 1, 5, and 9 of a 7 week cycle. Patients with neoplasms refractory to standard therapy or those for whom there is no standard therapy that is potentially curable or capable of extending life expectancy, will be evaluated for study eligibility without consideration of race, ethnic origin, sex or sexual orientation. The starting dose will be 20 mg/m2, defined using 1/10 of the MTD in preclinical animal studies. This will be escalated utilizing a modified Fibonacci scheme and toxicity endpoints will be evaluated utilizing the NCI common toxicity criteria. In addition, to the evaluation of the toxicity and pharmacokinetics of SarCNU, the study will look for evidence of clinical antineoplastic activity.
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