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 present phase II study was undertaken to assess antitumoral activity, safety and tolerability of recombinant human interleukin-6 (rh IL-6) in patients with advanced renal cell cancer. Rh IL-6 was administered as a daily subcutaneous injection at a fixed dose of 150 micrograms/day for a maximum of 42 consecutive days. 12 patients with metastatic renal cell cancer without previous immunotherapy were enrolled and were evaluated for response. No objective clinical responses were observed in the trial. Toxicity was moderate and reversible and mainly comprised fever, influenza-like symptoms, fatigue and moderate hepatotoxicity. Anaemia, leucocytosis, thrombocytosis and induction of an acute phase response were observed in most patients. In conclusion, prolonged subcutaneous administration of rh IL-6 on an outpatient basis is safe and feasible. However, rh IL-6 exhibited no antitumoral activity in patients with metastastic renal cell cancer. Profound regulatory effects on haematopoiesis and inflammatory response of rh IL-6 were observed.
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PMID:Lack of efficacy of recombinant human interleukin-6 in patients with advanced renal cell cancer: results of a phase II study. 971 86

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.
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PMID:Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. 981 99

Methotrexate-albumin conjugate (MTX-HSA) is a novel human albumin-based prodrug conjugate of methotrexate (MTX). A low MTX loading rate provided optimal tumor targeting and therapeutic efficacy during preclinical testing. The objectives of this first Phase I study of MTX-HSA were to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) in a weekly regimen. Seventeen cancer patients who were no longer amenable to standard treatment were enrolled and were evaluable for DLT. Up to eight injections were performed in weekly intervals. Dose escalation was as follows: 20, 40, 50, and then 60 mg/m2 MTX-HSA (based on the amount of MTX bound to albumin). Additional MTX-HSA courses were feasible in case of tumor response. DLT (mainly stomatitis, Common Toxicity Criteria grade 3) occurred, beginning at the 50 mg/m2 dose level after repeated administrations; in one case, thrombocytopenia was dose-limiting. Two events of DLT occurred at the 60 mg/m2 dose level within the first two administrations. Mild anemia, transaminitis, and one case of skin toxicity were found. No significant leukopenia, nausea, renal toxicity, or other toxicities were observed. MTX-HSA was well tolerated. Drug accumulation occurred on the weekly schedule. The half-life of the drug was estimated to be up to 3 weeks. Tumor responses were seen in three patients: (a) a partial response was seen in one patient with renal cell carcinoma (response duration, 30 months, ongoing); (b) a minor response was seen in one patient with pleural mesothelioma (response duration, 31 months, ongoing); and (c) a minor response was seen in one patient with renal cell carcinoma (response duration, 14 months until progression). Poststudy treatment was administered at 2-4-week intervals. No signs of toxicity or drug accumulation were seen. Altered pharmacological properties of MTX-HSA such as plasma half-life, tumor targeting, or intracellular metabolism might have contributed to these responses. The MTD for weekly administration was 4 x 50 mg/m2 MTX-HSA during short-term treatment. A regimen with MTX-HSA injections of 50 mg/m2 every 2 weeks was recommended for a further clinical Phase I study.
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PMID:Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society. 1021 9

A 75-year-old male presented to our hospital with a complaint of macroscopic hematuria. Laboratory examinations in peripheral blood showed slight anemia and the increase of acute phase reactants (c-reactive protein, immunosuppressive acidic protein, alpha 2-globulin). Abdominal enhanced computerized tomography revealed a huge tumor with calcification at the upper pole of the right kidney. Magnetic resonance imaging (MRI) showed a low intensity mass at the upper portion of the right kidney on T2-weighted sequences. The right radical nephrectomy was performed and the histopathological diagnosis was sarcomatoid renal cell carcinoma because of positive immunohistochemical staining for vimentin and negative for cytokeratin. Because sarcomatoid type has a highly malignant behavior and poor prognosis among renal cell carcinomas, an adjuvant treatment which is effective in controlling the disease is awaited.
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PMID:[Sarcomatoid renal cell carcinoma: a case report]. 1087 54

A 48-year-old man presented with recurrent gastrointestinal bleeding and anemia. Routine endoscopic evaluation was nondiagnostic. Angiography demonstrated multiple apparent arteriovenous malformations. Exploratory laparotomy revealed numerous splenic implants along the small and large bowels, some of which had apparently eroded through the bowel mucosa and bled. Excision of these penetrating lesions prevented further bleeding. An incidentally noted renal cell cancer was also resected. The patient's splenosis was the result of childhood trauma that caused splenic rupture and precipitated splenectomy. Splenosis develops frequently following traumatic splenic rupture. Experimental evidence suggests that the presence of an intact spleen suppresses the growth and development of splenic implants. Following splenectomy, splenules may replace some of the "housekeeping" and immunologic functions of the spleen, but even patients with documented splenosis should be considered functionally hyposplenic. While in most cases splenules cause no symptoms, splenosis must be considered in the differential diagnosis of previously splenectomized patients who present with unexplained masses or occult bleeding.
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PMID:Splenosis presenting as occult gastrointestinal bleeding. 1093 65

The authors report on the cases of two adult male patients presenting with autoimmune cytopenias associated with malignancies: a case of autoimmune haemolytic anemia occurring after remission of Hodgkin's disease and a case of autoimmune neutropenia in the setting of renal carcinoma. High-dose intravenous immune globulins (IIG) administered after failure of corticosteroid therapy produced a rapid and long-lasting response. These cases illustrate that intravenous immunoglobulins may be helpful in refractory cases of autoimmune cytopenias. The association of IIG and corticosteroid could be synergistic and effective independently of the outcome of the underlying disease. The pathophysiogenic mechanisms and literature are discussed briefly.
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PMID:Autoimmune cytopenias associated with malignancies and successfully treated with intravenous immune globulins: about two cases. 1096 14

We report one case of solitary gastric metastasis from renal cell carcinoma following radical excision of the primary tumour 14 years previously. During evaluation for a severe anaemia with melaena, a patient underwent upper gastrointestinal endoscopy that evidenced the presence of a small polypoid lesion in the body of the stomach. Endoscopic biopsy revealed renal cell carcinoma. There was no evidence of further metastatic disease. A subtotal gastric resection with Roux-en-Y gastrojejunal reconstruction was performed. After 6 months follow-up, the patient was disease-free. This case confirms the potential of renal cell carcinoma for late and solitary metastasis with circumscribed local invasiveness and suggests that endoscopic resection may be feasible.
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PMID:Gastric metastasis from renal cell carcinoma fourteen years after radical nephrectomy. 1114 27

We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 microg/m(2) daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood. 2001;97:1942-1946)
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PMID:A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma. 1126 56

Over a period of ten years (July 1988 to June 1998) all the patients seen at two health institutions in Enugu metropolis, with histologically diagnosed renal cell carcinoma, were studied to elucidate the pattern of presentation, management and response to treatment. Seventy four (74) such patients were seen during the study period. Fifty two (70.3%) were males while 22 (29.7%) were females. The ages of the patients ranged between 17 years and 72 years with a mean of 44 years. The commonest features at presentation were weight loss (100%) raised ESR (94.6%), haematuria (86.5%), anaemia (66.2%) and upper quadrant mass (64.9%). No bilateral case was encountered. Thirty two patients (43.2%) presented with the clinical triad of haematuria, loin pain and renal mass. Seven patients (9.5%) were HIV positive. Fifty nine patients (79.7%) presented with stages 3 and 4 disease and the outcome was poor. Those that presented with stages 1 and 2 tumour had good prognosis. Early diagnosis of the tumour is important in order to give the patients a high chance of survival.
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PMID:Renal cell carcinoma in Enugu, Nigeria. 1139 35

The evaluation of know prognostic factors is an essential step of the assessment of the patients affected by primary renal carcinoma. As long as the major biological mechanisms of renal carcinomas remain unknown, it will be impossible to achieve an accurate prognostic judgement. The TNM classification has always been the main source of information. Nevertheless, recently several investigations evaluated the prognostic power of serum and cellular markers. The aim of this study is to identify those markers which show statistical reliability and can be used in the clinical practice. A literature search was performed on MEDLINE to identify potential not traditional prognostic factors for patients with renal cell carcinoma edited from January 1997 through April 2000 using prognosis and clear cell carcinoma and kidney as keywords. We considered also articles cited in references of first selected manuscript. The analysis of serum and cellular prognostic markers does not allow the identification of specific factors, reliable, independent, easy to dose, widely useful and whose informations are repeatable. Currently classical prognostic factors (staging, grading, hystologic type, patient clinical conditions, anaemia, presentation modalities, etc.) represent the only useful elements after surgical time in RCC patients. Among serum prognostic factors, CRP and ferritin play a crucial role. These proteins appear ideal in monitoring the disease over time, due to simple test execution and specimens repeatability. Among RCC molecular markers, proliferation index result promising for their reliability and reproducibility, the easy dosage and high series number tested. Literature data suggest that the ideal marker for renal carcinomas has not been identified yet. However, C-reactive protein, ferritin and the proliferative activity indexes (Ki67 and AgNOR) appear to be, at present, the best prognostic tools. To confirm obtained results and to use biomolecolar markers on a routinary base further studies on wide surgical series will be required. The improvement of technical tool and costs reduction represent also a necessary step toward the identification of efficient prognostic markers in RCC.
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PMID:Not traditional prognostic factors in human conventional renal carcinoma. 1175 49


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