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  • 1
    ISSN: 1432-0843
    Keywords: Glutathione ; Glutathione transferase ; Resistance ; Modulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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 melphaln 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 μg/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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: multiple myeloma ; glucocorticoid receptors ; prednisone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Background: Prednisone is an active drug in the treatment of multiple myeloma. The optimal dose, frequency, and role of glucocorticoid receptors (GR) in response to prednisone is unknown.Purpose: The purposes of this study were (1) to estimate the response rate of alternate-day high dose prednisone in patients with relapsing and refractory multiple myeloma; (2) to measure the range of GR levels; and (3) to correlate the response of prednisone with GR status.Patients and methods: Between 8/86 and 1/90, 127 patients were entered onto the study with 121 evaluable for response. The number of GR sites/cell was determined on mononuclear cells isolated from pretreatment bone marrow aspirates using a one point GR binding assay. Patients received prednisone 100 mg po qod x 2 weeks, followed by 50 mg po qod x 10 weeks.Results: The overall response rate was 10% (95% CI: 5–15%) with a median survival of 11.8 months. The GR sites/cell ranged from 0–53,212 with a mean of 8,371 sites/cells. Stratification of GR sites into 0–2,500, 2,501–6,000 and 〉 6,000 sites/cells was associated with a response rate of 6%, 27% and 4% respectively (p = 0.009). The median survival of patients in these categories was 8.1, 14.9 and 10.6 months respectively. This was not significant by the logrank test (p = 0.11). Although myeloma patients with intermediate levels of GR sites/cell initially responded more favorably to prednisone, their long-term survival was not significantly improved.Conclusions: Alternate-day high-dose prednisone was well tolerated and may provide palliative benefit for a subset of patients with relapsing and refractory multiple myeloma. The survival of patients on this study was comparable to that reported with other but more toxic doses of glucocorticoids.
    Type of Medium: Electronic Resource
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