Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.
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PMID:[The clinical phase I study of TNP-351. The TNP-351 Research Committee]. 785 2

5-methyltetrahydrofolate (MTHF) is a main serum metabolite of 5-formyltetrahydrofolate (folinic acid, FA), a standard agent for potentiation of the cytotoxic activity of 5-fluorouracil (5-FU). The clinical application of MTHF instead of FA as a precursor of the biologically active metabolite 5,10-methyltetrahydrofolate (mTHF) is based on favorable pharmacologic characteristics of MTHF described so far. In this phase I study 18 patients with advanced solid malignancies were treated with MTHF for 5 days at doses ranging from 100 to 500 mg/m(2)/day in combination with a fixed dose of 500 mg/m2/day 5-FU given as a 4-hour infusion. The treatment was repeated after 21 days. The toxicity observed was mainly gastrointestinal with loss of appetite, nausea and vomiting (up to WHO grade III), and less frequently stomatitis, decline of hemoglobin and hematuria (up to WHO grade II). The frequency and severity of side effects seen were not related to the dose of MTHF. Cumulative toxicity was not observed. The MTD was not reached up to an MTHF dose of 500 mg/m(2)/day. Objective remissions were not seen. The study was terminated on the basis of results showing comparable 5,10-methylenetetrahydrofolate (mTHF) tumor- and tissue levels after administration of MTHF or FA.
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PMID:Phase-I tolerability study of 5-methyltetrahydrofolate in combination with a 4-hour infusion of 5-Fluorouracil in cancer-patients. 2155 7

We conducted a phase I/II trial of 5-fluorouracil (5-FU), calcium leucovorin (LV), zidovudine (AZT) and dipyridamole (DP), (FLAP) in patients with metastatic colorectal cancer, renal cell carcinoma and malignant melanoma. AZT and DP were given to enhance the biochemical modulation and antitumor activity of 5-FU and LV. All patients received 5-FU (370 mg/m(2) i.v. bolus day 0-4), LV (50 mg/m(2) p.o. every 4 h day 0-4) and DP (50 mg/m(2) p.o. every 6 h days 0-27). In the phase I portion of the study, AZT was dose escalated in cohorts of 5 patients each, from 50 mg p.o. every 6 h days 0-27 to the MTD of 200 mg p.o. every 6 h days 0-27. Thirty-three patients received 200 mg of AZT in the phase II portion of the trial. Eleven patients developed grade III and 5 patients developed grade IV leukopenia. Four patients developed grade III and 21 patients developed grade IV neutropenia, with six febrile neutropenic episodes. Six patients experienced grade III anemia and four grade III thrombocytopenia. Diarrhea or stomatitis of greater than or equal to grade III occurred in six and four patients, respectively. Fifty-eight percent (19 of 33) of patients required dose reductions of AZT for hematologic toxicity (13 of 19 in the first treatment cycle). At the 200 mg AZT dose level, there were two partial responses in nine colorectal cancer patients (22%), no objective responses in 14 patients with renal cell carcinoma or in 14 patients with melanoma. FLAP does not have significant activity in melanoma, renal cell carcinoma or 5-FU-treated colorectal cancer patients, although it may have activity in untreated colon cancer.
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PMID:Phase i/ii trial of 5-Fluorouracil, leucovorin, Zidovudine and dipyridamole for patients with metastatic colorectal-cancer, renal-cell carcinoma and malignant-melanoma. 2155 74