Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three).
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PMID:Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation. 705 68

Methylglyoxalbisguanylhydrazone or MGBG is an agent with a unique mechanism of action (polyamine biosynthesis inhibition). MGBG was discarded in the 1960s because of severe mucositis and other toxicities. New clinical trials in the late 1970s and early 1980s utilized weekly administration and indicated MGBG had significant activity in patients with chemotherapy-refractory Hodgkin's and non-Hodgkin's lymphoma. In addition, some activity was noted in patients with head and neck, prostate, esophageal, and endometrial cancer. The toxicities on the weekly schedule were minimal and no myelosuppression was noted. Based on MGBG's spectrum of antitumor activity and its activity in severely debilitated patients, we hypothesize that MGBG may have greater antitumor activity in patients who are malnourished (possibly based on polyamine depletion). MGBG is a good candidate for treatment of AIDS-associated NHL because it has proven activity in patients with NHL which is not associated with AIDS, crosses the blood brain barrier, is non-myelosuppressive, and appears to work in patients with inanition (no polyamines available to reverse MGBG's antitumor effects). Clinical trials are ongoing to determine the activity of MGBG in AIDS-associated NHL and other diseases. Based on encouraging initial results, it appears MGBG may become part of our therapeutic armamentarium.
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PMID:MGBG: teaching an old drug new tricks. 791 20