Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, a 13-week oral repeated dose toxicity study and a recovery study using male and female rats was conducted. Doses of S-1 were adjusted to deliver 1.5, 5, and 15 mg/kg/day as doses of FT, and FT was given at 15 mg/kg/day. The following results were obtained. 1. In clinical observation, edema of the limbs and face or swelling of the auricle of the ear and an anemic appearance were observed in both sexes in the 15 mg/kg/day group as dose of FT. Subsequently, males in this group developed severe anemia, decreased spontaneous motor activity, emaciation, and subnormal skin temperature, and many males died. In the survivors, keratosis of the palm, sole, or tail was observed, with necrosis and loss of the tail tip in the severe cases. 2. Body weight gain was suppressed from about week 2 of treatment in both sexes in the 15 mg/kg/day group as dose of FT, and there was almost no weight gain after week 4-5. Food consumption was consistently less than the control value for males in the 15 mg/kg/day group as dose of FT throughout the treatment period. 3. No marked changes were observed in water intake and on opthalmologic examination. 4. In the fecal test for occult blood, a positive tendency was observed in both sexes in the 15 mg/kg/day group as dose of FT. 5. Urinalysis disclosed a slight increase in protein and decrease in sodium, potassium, and chloride in males, and an increase in protein in females in the 15 mg/kg/day group as dose of FT. 6. Hematologically, both sexes in the 15 mg/kg/day group as dose of FT showed decreases in red blood cell count, hemoglobin, and hematocrit, and increases in platelet count and fibrinogen, with a slight decrease in white blood cell count in males. 7. In the blood biochemical test, abnormal findings included increases in total cholesterol and free cholesterol, and decreases in non-esterified fatty acid and albumin in both sexes in the 15 mg/kg/day group as dose of FT. 8. In organ weight measurement, abnormal changes included a decrease in thymus weight in both sexes in the 5 mg/kg/day or higher dosage groups and a decrease in the testis weight in males and an increase in the liver weight in females in the 15 mg/kg/day group as dose of FT. 9. Histopathologically, both sexes in the 15 mg/kg/day group as dose of FT showed a decrease in the red pulp of the bone marrow, atrophy of the thymus, white pulp of the spleen, and testes. degeneration of the renal tubules, and ulcerative changes of the skin or oral mucosa. 10. The findings were unremarkable in the FT group. 11. During the recovery study, all the toxic effects tended to reverse. 12. The NOAEL of S-1 was estimated to be 1.5 mg/kg/day as dose of FT for both sexes.
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PMID:[A 13-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in rats]. 902 59

TS-1, a novel oral formation of 5-fluorouracil, consists of 1 M tegafur (5-FU), 0.4 M CDHP and 1 M Oxo. The response rate in the late phase II study was reported as 49% in the patients with advanced gastric cancer. We report two patients with metastases from gastric cancer who markedly responded to TS-1. CASE 1: A 74-year-old man who suffered abdominal tumor was admitted to our hospital. Computed tomography (CT) showed advanced gastric cancer with huge liver metastases and extensive lymph node metastases. After 120 mg of TS-1 was orally administered for 12 weeks, CT showed a 77% reduction in the liver metastases. No serious adverse reactions were observed. CASE 2: A 66-year-old man had undergone a curative distal gastrectomy with D2 lymphadenectomy. One year later, CT showed enlargement of paraaortic lymph nodes due to cancer recurrence. There were no metastatic lesions in the other organs. After 100 mg of TS-1 was orally administered for 4 weeks, CT revealed that almost complete reduction of the metastatic nodes was obtained. Adverse reactions at grade 2 for leucopenia and anemia were observed. In conclusion, TS-1 was effective and well tolerable for patients with advanced gastric cancer.
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PMID:[Two cases of advanced gastric cancer responding to TS-1: a novel oral formation of 5-fluorouracil]. 1096 3

TS-1, a novel oral formation of 5-fluorouracil that consists of 1M tegafur (5-FU), 0.4M CDHP and 1M Oxo, is reported to achieve a higher response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of recurrent gastric cancer that responded significantly to the short-term administration of TS-1. A 73-year-old man, who had undergone a curative distal gastrectomy with D2 lymphadenectomy 2 years earlier, had presented with obstructive jaundice resulting from cancerous lymphadenopathy. PTCD was performed for drainage, but cholestasis disappeared completely through the two courses of oral administration of TS-1. The serum level of transaminase and bilirubin remained within normal limits, even with PTCD unequipped, until the patient died of the original disease. The adverse effects observed with the drug were anemia (grade 1) and skin pigmentation (grade 2), both of which improved soon after discontinuing the medication. In conclusion, TS-1 may be well-tolerable and effective in some cases of terminal-stage and/or recurrent gastric cancer, especially those associated with obstructive jaundice arising from the cancerous lymphadenopathy, in that patient QOL can be maintained to a much greater extent.
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PMID:[Case report: a recurrent gastric cancer in the terminal stage, associated with obstructive jaundice which responded significantly to oral administration of TS-1]. 1168 Dec 55