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)

Fourteen patients previously treated with surgery, radiotherapy, and/or chemotherapy for primary squamous cell carcinoma of the head and neck were treated with 4'-O-tetrahydropyranyl-Adriamycin (THP-adriamycin) for locally or distantly recurrent disease. The starting dose was 60 mg/m2 by i.v. infusion, with courses repeated every 3 to 4 weeks. A total of 34 courses of treatment were delivered (median, 2; range, 1-6). All patients were evaluable for response and toxicity. There were no responses. Severe (grade 3 or 4) neutropenia occurred in 11 patients. Thrombocytopenia, anemia, and gastrointestinal toxicity were modest, and no hepatic, renal, or cardiac toxicity was observed. The lack of response in association with severe neutropenia and moderate other toxicities using this dose and schedule of THP-Adriamycin should be taken into consideration prior to the pursuit of further study of this compound in a similar patient population.
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PMID:Phase II clinical trial of 4'-O-tetrahydropyranyl-adriamycin (THP-adriamycin) in recurrent squamous cell carcinoma of the head and neck. 202 88

4'-O-Tetrahydropyranyl adriamycin (THP adriamycin) is a new anthracycline active as a single drug in advanced breast cancer. We have undertaken a phase II study as first-line treatment for metastatic disease with THP adriamycin day 1 = 40 mg/m2 i.v. bolus and 5-fluorouracil day 1 to day 5 = 750 mg/m2 as a continuous i.v. infusion. The dose of THP adriamycin was further escalated up to the maximal tolerated dose defined as grade 3 granulopenia for each patient. Thirty-nine patients were included, 37 being so far evaluable for toxicity and for efficacy. The mean number of cycles given was 5 (range: 2-12). The overall response rate (CR + PR) was 54% (95% CI: 37.9-70.1) and the CR rate 8%. Sites of response were as follows: lung 6/9, liver 11/18, breast 4/8, nodes 7/14, skin 3/8, bone 2/8. Neutropenia with grade 3 + 4 nadir values was observed in 70.2% of the patients according to the objective of the study. No severe thrombopenia or anemia occurred. Stomatitis grade 3 was seen in 27% and grade 4 in 3% of the patients. Alopecia grade 2 was seen in 18% and grade 3 in 9%. No other toxicity was observed. We conclude that this association is effective in metastatic breast cancer, giving few alopecia. A high response rate in liver metastases warrants further evaluation.
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PMID:Association of bolus tetrahydropyranyl adriamycin and 120 hours continuous 5-fluorouracil infusion in patients with metastatic breast cancer. 229 56

The clinical pharmacology and toxicity of a novel anthracycline derivative, 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), was investigated in patients with advanced malignant diseases. The starting dose was 30 mg/m2 which was escalated by increments of 10 mg/m2. Twelve patients with a median age of 42 (range, 19-69) years and a median Eastern Cooperative Oncology Group performance score of 2 (range, 1-2) were entered into the study. The diagnoses included four testicular cancers, two breast cancers, two small cell lung cancers, two acute myeloid leukemias, one colon cancer, and one hemangiosarcoma. THP-adriamycin was given as an i.v. bolus injection every 3 weeks. Evaluable were 18 courses for general toxicity, 16 courses for hematological toxicity, and 16 courses for pharmacokinetics. THP-adriamycin had a short initial half-life of 1.4 +/- 0.3 min (mean +/- SD) due to rapid cellular uptake. Peak concentrations in unseparated blood cells were reached 5 min after drug injection and remained higher than in plasma throughout the observation period of 72 h. The half-lives of THP-adriamycin in plasma were 19 +/- 2.8 min in an intermediate and 13 +/- 1.6 h in the terminal phase. A linear correlation was observed between the dose and the areas under the concentration curves for THP-adriamycin in plasma (r2 = 0.97) and blood cells (r2 = 0.99). The volume of distribution was 2124 +/- 221 liters/m2 and the total clearance rate 115 +/- 11 liters/m2h. THP-adriamycin was metabolized to Adriamycin, THP-adriamycinol, and adriamycinol. The major metabolite was Adriamycin with a terminal half-life in plasma of 33 +/- 10 h. The area under the curve of Adriamycin was also correlated to the administered dose (r2 = 0.96). Since excessive peak concentrations of Adriamycin were avoided, the treatment with THP-adriamycin might be an alternative to continuous infusions or weekly administrations. The maximum tolerated dose was 70 mg/m2, and the dose-limiting toxicities were leukopenia and thrombocytopenia. Anemia, nausea, and vomiting were mild to moderate, and no other toxicity was observed. All side effects were dose dependent and reversible. In a patient with breast cancer, a disease stabilization was achieved lasting for 9 weeks. No objective remission was observed. We suggest 60 mg/m2 in pretreated or poor risk and 70 mg/m2 in untreated or good risk patients every 3 weeks for further clinical trials.
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PMID:Clinical pharmacology and toxicity of 4'-O-tetrahydropyranyladriamycin. 381 48

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).
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PMID:Clinical and pathological response to primary chemotherapy in operable breast cancer. 929 6

Tumor necrosis factor alpha (TNF-alpha) has multiple effects on iron homeostasis and erythropoiesis and has been implicated in the pathogenesis of the anemia of inflammation. We postulated that intracellular iron in turn may regulate the expression of TNF-alpha. In the human monocytic leukemia cell line, THP-1, low basal TNF-alpha message levels were stimulated (sevenfold) when serum was excluded from the culture medium. Addition of hemin completely suppressed TNF-alpha expression. Similarly, hemin suppressed lipopolysaccharide-induced expression of TNF-alpha. Sn-protoporphyrin, an inhibitor of heme oxygenase (which releases iron from hemin), prevented hemin-induced suppression of TNF-alpha expression. Conversely, the intracellular iron chelator, desferrioxamine, stimulated TNF-alpha expression. Thus, the expression of TNF-alpha, itself a physiological regulator of iron homeostasis, appears to be controlled by intracellular levels of iron.
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PMID:Suppression of TNF-alpha gene expression by hemin: implications for the role of iron homeostasis in host inflammatory responses. 933 26

A 68-year-old woman was admitted in March 1997 because of lumbago, fever, vomiting, and general malaise. Laboratory data disclosed anemia and severe hypercalcemia (7.7 mEq/l). Multiple osteolytic lesions were detected in the patient's vertebra, pelvis, and bilateral tibia by x-ray films and 99mTc bone scintigrams. Bone marrow aspiration sample was not obtained due to dry tap. Marked myelofibrosis and proliferation of lymphoid cells were revealed by a bone marrow biopsy specimen. Immunohistochemical analysis showed that cells in the biopsy specimen were positive for L-26 and LCA, but not for UCHL-1. Gastrointestinal endoscopic examination found multiple polypoid lesions in the stomach; biopsy specimens of the lesion tissue disclosed invasion by B lymphoid cells. A diagnosis of diffuse large B cell lymphoma was thus made. THP-COP chemotherapy was performed, but only minimal response was obtained. Lymphoma cells subsequently invaded the brain stem, and the patient eventually died of respiratory failure.
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PMID:[Extranodal non-Hodgkin's lymphoma associated with systemic bone metastasis and secondary myelofibrosis]. 1002 51

We retrospectively compared therapeutic results and adverse events in 198 elderly patients (> or = 70 yr old) with aggressive non-Hodgkin's lymphoma diagnosed between 1981 and 1995 who underwent CHOP, COP-BLAM, COP-BLAM III, or THP-COPBLM chemotherapy. Complete remission (CR) was achieved in 138 patients (69.7%). The CR rate was 47.0% for CHOP, 76.3% for COP-BLAM, 67.9% for COP-BLAM III, and 74.4% for THP-COPBLM therapy (p = 0.013). The 5-yr survival rate was 37.0% for CHOP, 49.0% for COP-BLAM, and 53.5% for COP-BLAM III. The event-free survival rate showed no significant differences between the four treatments. Adverse events of Grade 3 or worse were commonly anemia or granulocytopenia in patients receiving THP-COPBLM therapy. Cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with pirarubicin than with doxorubicin. For elderly patients, it is better to select therapy with as few adverse events as possible based on the complications and medical history of the individual patients.
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PMID:Response and adverse drug reactions to combination chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma: comparison of CHOP, COP-BLAM, COP-BLAM III, and THP-COPBLM. 1058 May 66

In the treatment of 2 patients with recurrent gastric cancer who showed bone metastasis and lymph node recurrence, we administered 30 mg/body of pirarubicin (THP) on the first day of treatment, and 30 mg/body of cis-platinum (CDDP) and 500 mg/m2 of 5-fluorouracil (5-FU) for 3 days (FP therapy). Marked effects were achieved. Gastric cancer of Borrmann IV type was diagnosed in Case 1, and total gastrectomy was performed. The histological type was poorly differentiated adenocarcinoma, and the histological classification was II. A bone metastasis was found three years after operation. The patient was CR after three courses of treatment, and has survived for 2 years. In Case 2, advanced gastric cancer was treated with neoadjuvant chemotherapy and distal gastrectomy. The histological type was moderately differentiated adenocarcinoma, and the histological classification was IIIa. Obstructive jaundice due to lymph node recurrence developed 6 years after operation. Two courses of treatment were provided after PTCD, and PR was observed. The patient has survived for 3 months. Both patients exhibited mild side effects such as anemia and leukocytopenia, but no serious complications were observed. Although various dosage regimens of FP therapy have been investigated, there has been a certain limit to the response rate achieved by this therapy, and new protocols have been explored. We achieved marked effects in 2 patients by adding THP to FP therapy. These cases are reported here together with some discussion of cases reported in the literature.
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PMID:[Two cases of recurrent gastric cancer for which combination chemotherapy with pirarubicin, cis-platinum and 5-fluorouracil were markedly effective]. 1066 Jul 42

Anemia is frequently observed in patients suffering from chronic inflammatory disorders. Recent in vitro data suggest that Th2 cytokines, such as IL-10, could be involved in its pathogenesis. We analyzed 1) changes in hemoglobin values in 329 patients with chronic active Crohn's disease receiving the anti-inflammatory cytokine IL-10 as part of a randomized, double-blind, placebo-controlled study, 2) serum iron parameters in a subgroup of these patients (n = 54), and 3) the in vitro effects of IL-10 on ferritin transcription and translation in human monocytic cells (THP-1) by means of Northern blot and immunoprecipitation after metabolic labeling. Patients receiving higher doses of IL-10 developed anemia and presented with a dose-dependent increase of ferritin and soluble transferrin receptor levels, an indicator of iron restriction to erythroid progenitor cells. According to our in vitro data, hyperferritinemia may result from direct stimulation of ferritin translation by IL-10 in activated monocytic cells, most likely by cytokine-mediated reduction of the binding affinity of translational repressors, iron-regulatory proteins, to the 5'-untranslated region of ferritin mRNA. In patients, all observed changes were most pronounced at the end of therapy (day +29), and thereafter hemoglobin levels and serum iron parameters returned to baseline levels within 4 wk of follow-up. Our data demonstrate that IL-10 causes anemia in patients with inflammatory bowel disease which may be referred to the induction of imbalances in iron homeostasis by the cytokine, leading to hyperferritinemia and limited iron availability to erythroid progenitor cells, a condition typically seen in the anemia of chronic inflammation.
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PMID:Role of IL-10 for induction of anemia during inflammation. 1216 51

The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.
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PMID:Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level. 1235 90


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