Activity of melphalan in combination with the glutathione transferase inhibitor sulfasalazine.

Abstract:

:Glutathione (GSH) transferases (GST), a family of detoxification enzyme proteins, are suggested to play an important role in tumor cell resistance to melphalan. The GST-activity inhibitor ethacrynic acid has been shown to increase the antitumor activity of melphalan in vitro as well as in vivo. In this study we determined the activity and toxicity of melphalan in combination with another GST-activity inhibitor, sulfasalazine, an agent used to treat ulcerative colitis. We entered 37 previously treated patients with advanced cancer of different histologies on sulfasalazine given at the individually calculated maximum tolerated dose (MTD) and melphalan given at doses beginning at 20 mg/m2. The main toxicity arising from this combination was nausea and vomiting, whereas increased myelosuppression was not observed. A partial response was seen in 2/4 of the ovarian cancer patients only. Plasma sulfasalazine levels varied between 2.5 and 47.1 micrograms/ml. Although reductions in GSH/GST levels were observed in peripheral mononuclear cells of certain patients following sulfasalazine treatment, there was no correlation between the extent of reduction and the plasma sulfasalazine level. A larger patient population must be studied to determine the usefulness of this combination.

authors

Gupta V,Jani JP,Jacobs S,Levitt M,Fields L,Awasthi S,Xu BH,Sreevardhan M,Awasthi YC,Singh SV

doi

10.1007/BF00685726

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

13-9

issue

1

eissn

0344-5704

issn

1432-0843

journal_volume

36

pub_type

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