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)

The use of [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)]propane (ICRF-187) as a protective agent against normal tissue toxicity caused by combined Adriamycin (ADR) and whole body hyperthermia (WBH; 2 h at 41.5 degrees C) was assessed in a rat model. The effect of ICRF-187 on the antitumor response induced by the combination of ADR and WBH was also investigated in order to assess alterations in the therapeutic index of this combined therapeutic modality treatment. ICRF-187 significantly reduced ADR-mediated body weight loss, renal toxicity, and cardiomyopathy under both normothermic and hyperthermic conditions as shown by morphological and functional assays. ADR-induced neuropathy (seen only in normothermic rats) was also ameliorated by ICRF-187. Although this study did not show a pronounced effect of ICRF-187 on ADR-induced acute myelosuppression, ADR-mediated chronic anemia, leukocytosis, and thrombocytosis were reduced by ICRF-187 in both normothermic and WBH-treated rats. The effect of ICRF-187 on antitumor response was evaluated with a tumor growth delay assay using an in vivo transplantable fibrosarcoma. ICRF-187 caused no significant change in tumor growth delay induced by either ADR alone or ADR combined with WBH. Indeed, the only complete tumor regression following treatment resulted from the combination of ICRF-187 plus ADR plus WBH. Thus, ICRF-187 significantly increases the therapeutic index of the combined modality treatment of ADR and WBH by selectively reducing normal tissue toxicity without interfering with antitumor efficacy.
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PMID:Protective effect of ICRF-187 against normal tissue injury induced by adriamycin in combination with whole body hyperthermia. 190 99

ICRF-187 was given to 62 evaluable patients with advanced solid tumors in a Phase I clinical trial. Weekly infusions were given in dosages ranging from 0.85 g/m2 to 7.42 g/m2 for a total of four weeks with a two week rest period between courses. Dose-limiting hematological toxicity was seen in heavily pretreated patients at a dose of 3.8 g/m2/week. All patients also developed reversible SGOT elevations. In patients with less prior therapy hematologic toxicity was not dose-limiting but hepatotoxicity, manifest by transient SGOT levels greater than 5 times baseline was seen at 7.42 g/m2/week even though only 3/6 patients could receive 4 consecutive weekly doses. At virtually all dose levels tested some patients developed anemia. Other toxicities, including alopecia, nausea, vomiting and reversible serum amylase elevations, were mild. Cumulative monthly doses achieved on this weekly schedule are significantly higher than a 48-hour infusion or daily times 3 or 5 schedule in adults and a daily times 3 schedule in children. Pharmacokinetic studies in eight patients indicate that the drug disappears from the plasma biphasically with a terminal t1/2 of 3.2 +/- 0.9 hr. The total clearance was 288.7 +/- 85.0 ml/hr/kg and the volume of distribution (Vda) was 1.3 +/- 0.4 l/kg. Pharmacokinetics were not dose-dependent from 3.8-7.4 g/m2 and no difference in pharmacokinetics was found in patients studied during the first and second treatments of a course. If Phase II trials of ICRF-187 are to be pursued on this schedule, appropriate doses would be 3.8 g/m2/week X 4 for heavily pretreated and 7.42 g/m2/week for "good risk" patients. Because of erratic hematologic toxicity in heavily pretreated patients, some might only tolerate three weekly doses. In good risk patients transaminitis was significant but reversible, thus, Phase II protocols should include dose escalation schemata.
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PMID:Phase I clinical trial and pharmacokinetics of weekly ICRF-187 (NSC 169780) infusion in patients with solid tumors. 311 12

Peripheral blood smears made during 2 studies of chemical antidotes for doxorubicin (DRB) cardiotoxicity in dogs were examined to determine the incidence of poikilocytosis. The 1st study had significantly (P less than 0.05) increased numbers of poikilocytes in 3 groups of 5 dogs, each treated with DRB alone, DRB plus thyroxine (0.5 mg/day), and DRB plus thyroxine (2.0 mg/day), respectively, compared with 1 group of 5 dogs treated with thyroxine alone (2.0 mg/day). In addition, the DRB-treated dogs had regenerative anemia characterized by an increased reticulocyte index. The 2nd study had a significant (P less than 0.05) increase in poikilocytes in 4 groups of 6 dogs, each treated with DRB alone, DRB plus +/- -1,2-bis(3-5-dioxopiperazinyl-1-yl; ICRF-187), DRB plus N-acetylcysteine (NAC), and drb plus ICRF-187 plus NAC, respectively, compared with 4 groups of 3 dogs, each treated with ICRF-187 plus saline solution (SS), NAC plus SS, ICRF-187 plus NAC plus SS, and SS alone, respectively. In both studies, the poikilocytes were identified as echinocytes, spiculated erythrocytes, and schizocytes. Administration of thyroxine and ICRF-187 did not prevent the occurrence of poikilocytosis in DRB-treated dogs. Administration of NAC with DRB resulted in a mild decrease in the extent of poikilocytosis compared with that observed in dogs given DRB alone. The hematologic changes observed in both studies were not accompanied by adverse clinical signs referable to the DRB-induced alterations in erythrocytes.
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PMID:Poikilocytosis in dogs with chronic doxorubicin toxicosis. 392 63

Single- and multiple-treatment schedule in dogs were used to evaluate the toxicity of ICRF-187. The major target organs were the bone marrow, lymphoid tissue, gastrointestinal tract, liver, and kidney. Liver, kidney, and intestinal toxic effects were most severe at lethal doses. Toxic effects on the kidney and intestinal tract were reduced or absent at lower doses. Hepatotoxicity was most severe after single doses and was only slowly reversible at high doses. Repeated dosage regimens had the greatest effect on circulating blood cells, and anemia and neutropenia were most prominent after three series of five daily doses with rest periods between series. ICRF-187 was more toxic to dogs in terms of total dose received when administered in five daily doses than in single doses. A rest period between series of five daily doses allowed a larger total dose to be administered.
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PMID:Preclinical toxicologic evaluation of ICRF-187 in dogs. 678 45