Abstract
20019 Background: Depletion of Arg using Arg deiminase results in cell death in melanoma cells. Lack of ASS, a key enzyme which can synthesize Arg from citrulline, explains why melanoma cells are sensitive to ADI-PEG20(Polaris Inc.). Our phase II trial of ADI-PEG20 showed activity in melanoma. With this clinical trial, we correlated ASS expression in tumor/primary culture (PC) before and at relapse. Methods: PC was established from biopsy prior or after treatment failure. ADI-PEG20 was given at 160 IU/m2 i.m weekly and escalated to 320 IU/m2 if Arg levels were detected. Tumor assessment was done every 8 wks. ASS was assayed by immunohistochemical (IH.) and/or real time PCR (RPCR.) The ratio of GADPH and ASS was calculated using sensitive/ resistant melanoma cell lines as control (efficiency of both primers sets are equal to 1). Results: 22 patients (pts) were accrued and were assessable for response. 4 pts (18%) had partial response (PR), 3 minor response, 3 mixed response and 1 stable disease. Thus, sign...
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