Final results of phase II trial of pegylated arginine deiminase (ADI-PEG20) in metastatic melanoma (MM).

Authors:
  • LFL. G. Feun
    L. G. Feun
  • MYM. You
    M. You
  • CWC. Wu
    C. Wu
  • MWM. Wangpaichitr
    M. Wangpaichitr
  • MKM. T. Kuo
    M. T. Kuo
  • AMA. Marini
    A. Marini
  • AJA. Jungbluth
    A. Jungbluth
  • NSN. Savaraj
    N. Savaraj
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Abstract
8528 Background: ADI-PEG20 catabolizes arginine (Arg), a nonessential amino acid in human adults, to citrulline and ammonia. Tumor cells which lack argininosuccinate synthetase (ASS) are unable to synthesize Arg which can lead to cell death. A phase I/II trial of ADI- PEG20 showed activity in MM (JCO 23:7660) and the optimum biologic dose (OBD) was considered to be 160 IU/m2/week which lowered blood Arg to nondetectable levels. In this phase II study, we obtained tumor samples, when accessible, for ASS staining prior to therapy in patients (pts) with MM and correlated the ASS staining with tumor response. Methods: MM pts were treated with ADI- PEG20 (provided by Polaris, Inc.) at 160-320 IU/m2 I.M. weekly. Tumor measurements were done every 8 weeks. Pretreatment tumor samples were available in 26 pts for ASS staining by immunohistochemistry and/or real time PCR. Results: 36 pts were evaluable for response. 4 (11%) had tumor shrinkage at > 30%, 4 had minor response (< 30% shrinkage), 2 had stable disease a...