Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-FU, semustine (MeCCNU), triazinate (TZT), and razoxane (ICRF-159) have each shown activity against advanced colorectal cancer in studies by at least two investigative groups. Objective response rates, however, have been low, without evidence of increased patient survival. The hope of this study was that enhanced activity might result from giving these agents in two-drug combinations. There were 167 eligible and evaluable patients randomized among the programs: 5-FU at a dose of 500 mg/m2/day by iv push X 5 (F); 5-FU at a dose of 400 mg/m2/day iv X 5 plus TZT at a dose of 175 mg/m2/day iv X 3 (FT); 5-FU at a dose of 400 mg/m2/day plus ICRF-159 at a dose of 600 mg/m2/day orally X 3 (FI); MeCCNU at a dose of 150 mg/m2/day orally plus TZT at a dose of 200 mg/m2/day iv X 3 (MT); MeCCNU at a dose of 150 mg/m2 orally plus ICRF-159 at a dose of 500 mg/m2/day orally X 3 (MI); and ICRF-159 at a dose of 425 mg/m2/day orally X 3 plus TZT at a dose of 125 mg/m2/day iv X 3 (IT). Patients with limiting conditions (serum creatinine greater than 1.5 mg/dl or elevated bilirubin) were randomized among programs F, FI, and MI. Objective response rates by treatment arm were: F--13% (four of 31 patients); FT--13% (four of 31); FI--15% (four of 27); MT--11% (three of 28); MI--13% (four of 32); and IT--6% (one of 17). Response rates of combination arms were not significantly larger than those of 5-FU alone. With regard to survival, patients initially treated with 5-FU alone had the most favorable experience (median, 10.8 mos). Multivariate analysis showed the following factors to have a significant and independent influence on survival: Eastern Cooperative Oncology Group performance score, grade, site of indicator lesion, and the presence of 5-FU in the treatment regimen. Toxic effects most frequently seen were nausea, vomiting, thrombocytopenia, leukopenia, diarrhea, stomatitis, alopecia, and dermatitis. The incidence and severity of toxicity were roughly comparable among the six treatment arms.
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PMID:Randomized phase II studies in advanced colorectal carcinoma: a North Central Cancer Treatment Group study. 664 May 51

ICRF-187 is the D-enantiomer of the racemic antitumor agent ICRF-159 and was selected for clinical trials on the basis of aqueous solubility suitable for iv administration. Eighteen patients with refractory advanced solid tumors received ICRF-187 by a 48-hour continuous iv infusion in 5% Dextrose in Water, USP. The total dose ranged from 200 to 1000 mg/m2/48 hours. Courses were repeated at 22--28-day intervals. The major toxic effect was reversible granulocytopenia, with the nadir on Day 12 and the recovery by Day 22. At a dose of 1000 mg/m2/48 hours, the median nadir total wbc count was 1700/mm3 (range, 1300--2600), and the median nadir granulocyte count was 597/mm3 (range, 270--1300). Platelet count nadirs of less than 100,000/mm3 occurred in only three of 16 courses at this level. Granulocyte toxicity was not cumulative and was less severe in repeated courses (median nadir, 1000/mm3 in courses two and three). Mild nausea, malaise, and three instances of alopecia were the only nonhematologic toxic effects encountered. Compared to other schedules, a continuous 48-hour infusion of ICRF-187 seems to have greater toxic effects for a given total dose, and this may predict greater biologic effect. A starting dose of 1000 mg/m2 by a 48-hour continuous infusion is recommended for phase II trials.
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PMID:Phase I trial of ICRF-187 by 48-hour continuous infusion. 678 40

ICRF-159, and EDTA derivative antitumor agent, was given to 21 patients with advanced gastric cancer in a weekly dose of 3000 mg/m2. Of the 21 patients, 11 had failed prior drug therapies and 10 were previously untreated. No patient achieved an objective partial response (actual response less than 15% with 95% confidence level). One previously treated patient had a minor response lasting 12 weeks and four patients (three previously untreated) had stable disease lasting 4-8 weeks. Toxicity was acceptable, consisting of mild nausea and moderate myelosuppression. Median survival after treatment was 17.5 weeks in previously untreated patients and 9 weeks in previously treated patients. We conclude that ICRF-159 is inactive in advanced gastric cancer when given on a weekly schedule.
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PMID:ICRF-159 in advanced gastric cancer. Absence of activity. 716 6