Gene/Protein Disease Symptom Drug Enzyme Compound
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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen patients with polycythaemia vera or essential thrombocythaemia were treated with interferon-alpha in order to normalize elevated platelets. Patients were followed for 6 months and the frequency and intensity of symptoms and side effects were recorded before and during the study period by the patients and by the doctor. Health-related quality of life was also assessed. The most frequently reported pretreatment symptoms were fatigue, headache and muscle pain. The intensity of fatigue initially increased during treatment and there was no relief of any of the three most frequent symptoms during the treatment period. Common interferon-related symptoms such as fever and chills were most frequently reported after one week. After one month of treatment, symptoms related to the gastrointestinal tract reached a peak. Two patients discontinued treatment during the study period. Another patient suffered severe depression after the study period when still on interferon. There was no difference between the frequency of symptoms recorded by the doctor and that reported by the patients.
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PMID:Symptoms, symptom distress and health-related quality of life in patients with polycythaemia vera or essential thrombocythaemia during treatment with interferon-alpha. 1199 May 18

A randomized, controlled, double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds. In all, 150 healthy men and women (aged 18-51 years) were randomly assigned to 1 of 3 groups: intranasal interferon (IFN)-alpha2b (6 x 10(6) U every 12 h x 3) plus oral chlorpheniramine (12 mg extended release) and ibuprofen (400 mg) every 12 h for 4.5 days (n=59 subjects); intranasal placebo plus oral chlorpheniramine and ibuprofen (n=61 subjects); or intranasal and oral placebos (n=30 subjects). Treatment was started 24 h after intranasal viral challenge. During the 4.5 days of treatment with IFN-alpha2b, chlorpheniramine, and ibuprofen, the daily mean total symptom score was reduced by 33%-73%, compared with placebo. Treatment reduced the severity of rhinorrhea, sneezing, nasal obstruction, sore throat, cough, and headache and reduced nasal mucus production, nasal tissue use, and virus concentrations in nasal secretions. IFN-alpha2b added to the effectiveness of chlorpheniramine and ibuprofen and was well tolerated.
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PMID:Combined antiviral-antimediator treatment for the common cold. 1213 49

Advanced renal cell carcinoma is a chemoresistant disease. Immunotherapy with alpha interferon or interleukin (IL)-2 has produced response rates of approximately 15%, but better treatments are needed. IL-4 is a cytokine produced by activated CD4+ lymphocytes and has pluripotent activities including inhibiting the in vitro proliferation of human renal cell carcinoma cell lines. In this trial, patients were required to have a histologic diagnosis of renal cell adenocarcinoma with measurable disease and performance status (SWOG) of 0-1. Patients had to have adequate bone marrow, renal, and hepatic function as well as no clinically significant pulmonary or cardiac dysfunction. IL-4 was given by subcutaneous injection at a dose of 5 micorg/kg/d, daily for 28 days followed by a 7-day rest period. Fifty-eight patients were registered with seven patients ineligible and two patients not analyzable because they did not receive treatment. In the 49 eligible and analyzable patients, there were no confirmed complete or partial responses. There was one unconfirmed partial response in retro-caval lymph nodes, but no verifying measurement was done. There were seven patients with stable disease, no response, 25 with increasing disease/progression, and 16 patients whose assessment was inadequate to determine response. The median time to progression was 3 months, and the median survival was 13 months. Toxicity was significant with the most common side effects nausea, vomiting, or diarrhea, followed by headache/pain and malaise/fatigue/lethargy. There were 13 instances of grade 4 toxicity that occurred in nine different patients. Unique toxicities included Bell's palsy in three patients and hypoglycemia in a previously well-controlled diabetic. Despite promising growth inhibitory and immunologic effects, IL-4 in this dose and schedule is not useful for the treatment of patients with disseminated renal cell carcinoma.
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PMID:Phase II trial of recombinant human interleukin-4 in patients with advanced renal cell carcinoma: a southwest oncology group study. 1214 58

This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.
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PMID:Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction. 1236 25

Recombinant human interleukin 12 (IL-12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)-based therapy are limited. Prior dose-ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL-12. The aim of this study was to determine the safety and efficacy of prolonged IL-12 therapy in patients who have failed treatment with IFN-alpha +/- ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN-alpha or combination IFN-alpha plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL-12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL-12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL-12 in an open-label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL-12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL-12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL-12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN-based therapy.
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PMID:A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. 1277 16

A survey was made on 10 patients with subacute sclerosing panencephalitis (SSPE) during the last four years from the viewpoint of clinical safety of ribavirin therapy in Japan. Although the age of onset, latent period, and effectiveness were variable among the cases, they were treated safely with intraventricular ribavirin combined with high doses of interferon (IFN). Their clinical stages on admission ranged from the first to fourth of Jabbour's classification, and those on the beginning of ribavirin therapy also ranged from the first to fourth. Seven of them were first treated with intraventricular IFN-alpha monotherapy, however, the combination of intraventricular IFN-alpha and ribavirin was started after clinical worsening. Although 5 patients showed slow progression, seven responded to the therapy with clinical improvement or decreased measles antibody titers in the CSF. Especially, one patient showed improvement to Jabbour's first stage and no further progression during the following 3 years. Ribavirin therapy caused no severe effects. Lip swelling (50%), sleepiness (40%), and headache (30%) were noted. Although we were unable to perform a double-blinded clinical study for ethical reasons, our results suggest that treatment with intraventricular ribavirin and high doses of IFN may be effective for SSPE. Early administration of intraventricular ribavirin and IFN might be considered especially to IFN in non-responders. To establish this combination therapy as a safe and effective treatment of SSPE, further studies are necessary on the role of ribavirin in the pathogenesis as well as its effects in the central nervous system.
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PMID:[Trial of intraventricular ribavirin and interferon-alpha combination therapy for subacute sclerosing panencephalitis (SSPE) in Japan]. 1287 9

Protein kinase C (PKC) has a critical role in several signal transduction pathways, and is involved in renal cancer pathogenesis. Bryostatin-1 modulates PKC activity and has antitumour effects in preclinical studies. We conducted a multicentre phase II clinical trial in patients with advanced renal cancer to determine the response rate, immunomodulatory activity and toxicity of bryostatin-1 given as a continuous 24 h infusion weekly for 3 out of 4 weeks at a dose of 25 mug m(-2). In all, 16 patients were recruited (11 males and five females). The median age was 59 years (range 44-68). Patients had been treated previously with nephrectomy (8) and/or interferon therapy (9) and/or hormone therapy (4) and/or radiotherapy (6). Eight, five and three patients had performance statuses of 0, 1 and 2, respectively. A total of 181 infusions were administered with a median of 12 infusions per patient (range 1-29). Disease response was evaluable in 13 patients. Three patients achieved stable disease lasting for 10.5, 8 and 5.5 months, respectively. No complete responses or partial responses were seen. Myalgia, fatigue, nausea, headache, vomiting, anorexia, anaemia and lymphopenia were the commonly reported side effects. Assessment of biological activity of bryostatin-1 was carried out using the whole-blood cytokine release assay in six patients, two of whom had a rise in IL-6 levels 24 h after initiating bryostatin-1 therapy compared to pretreatment values. However, the IL-6 level was found to be significantly lower at day 28 compared to the pretreatment level in all six patients analysed.
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PMID:A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer. 1456 10

Chronic hepatitis C virus infection is a common and serious disease. Although an estimated 2.7 million persons in the United States have this disease, most have not yet been diagnosed. Recent advances in treatment provide successful cure in 50 to 80 percent of cases. Current drug therapy consists of a combination of pegylated interferon and ribavirin. Although all patients with chronic hepatitis C virus infection are potential candidates for treatment, pharmacologic therapy has a number of contraindications. Evaluation of suitability for treatment includes a thorough search for comorbid medical and psychiatric conditions that can be contraindications. Initial testing involves anti-hepatitis C virus antibodies, but definitive diagnosis of active disease requires detection of viral RNA. Most patients require a liver biopsy to determine the amount of hepatic fibrosis and ongoing hepatocellular inflammation. Viral genotype also should be determined: type 1 requires 12 months of treatment and does not respond as well as types 2 and 3, which require only six months of treatment. Common side effects of drug therapy include anemia, anorexia, depression, fatigue, fever, headache, myalgia, nausea, and erythema at the injection site.
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PMID:Management of hepatitis C: evaluating suitability for drug therapy. 1586 91

The Kirkwood high-dose interferon-alpha2b adjuvant therapy in high-risk-of-recurrence melanoma patients (stage IIb-III) demonstrated a benefit in terms of disease-free survival (DFS) (three trials out of three) and overall survival (OS) (two trials out of three). These important and exclusive results match with a grade 3-4 toxicity in about 75% of patients. This problem is the most limiting of this treatment. The aim of the study was to check these results and the feasibility of this treatment using the original Kirkwood schedule of 52 weeks, with appropriate dose modification, until unacceptable toxicity or progression of disease. From 23rd February 1998 until 29th July 2002, 26 patients were treated (mean age 45 years; range 25-70) with high-dose interferon-alpha2b adjuvant therapy. All patients were evaluated for toxicity, whilst 24 out of 26 (92%) were evaluated for OS and DFS. All patients were in stage IIB/III of the new American Joint Committee on Cancer (AJCC) classification. The sentinel node biopsy was performed in 19 out of 26 (73.1%) patients (clinical N0). At 31st December 2002, 20 out of 26 (77%) were still alive, whilst four (15%) had died and two (8%) were lost to follow-up. Of the patients still alive, 14 (70%) were disease free. The patients lost to follow-up refused to continue therapy for toxicity related treatment: one of them was disease free, whereas one was relapsed. There were 11 observed relapses (44%). The DFS ranged from 2 to 27 months. Among the patients, the maximal DFS is, at the time of writing, 59 months. The DFS mean is 29 months, the median is 19 months. The OS calculation will be performed at the end of 5 years observation. Now our attention is on therapy tolerability. In 18 patients out of 26 (69%) we noted at least one grade 3-4 toxicity, in accordance with literature data. The most common toxicities were haematological, hepatic, fever and asthenia. Overall, only two grade 4 events (one hepatic and one haematological) were reported. Grade 3 toxicity was hepatic in 23% of patients and haematological in 50%. Grade 2 toxicity was hepatic in 19%, haematological in 27% and fever in 50%. Grade 1 toxicities were hepatic, haematological and fever in 15, 15 and 35% of patients, respectively. Asthenia was severe in 54%, mild in 31% and not found in 15%. In 39, 4 and 15%, respectively, we have reported no hepatic, haematological or fever events. Less common toxicities were nausea, diarrhoea, headache, arthralgia, alopecia and one case of hypothyroidism. As a result of these reported toxicities, of 23 patients evaluable with regard to the protocol, 12 underwent dose reductions, six suspended treatment for disease progression, eight delayed treatment for toxicity, two interrupted treatment indefinitely for unacceptable toxicity or refused treatment, two refused to continue, two patients had no delay in treatment and three did not receive any delay or dose reduction. Of three patients still in therapy, just one has so far received a delay in treatment. Overall, only four patients (17%) interrupted therapy for toxicity related events, whereas 83% continued with the expected program: 52 weeks of therapy with appropriate dose modifications.
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PMID:Feasibility of high-dose interferon-alpha2b adjuvant therapy for high-risk resected cutaneous melanoma. 1505 49

Availability of a drug regimen that eradicates the hepatitis C virus (HCV) in more than half of treated patients provides the medical community with a powerful new weapon to diminish the anticipated future wave of HCV-related liver disease and cancer. Clinicians must understand the benefits, risks, and costs associated with the combination of peginterferon alfa and ribavirin. Major clinical trials with this new standard of HCV therapy have demonstrated sustained virologic responses of 54% and 56% with 48 weeks of combination therapy. Response is highest in those with genotype 2/3, with early virologic response by week 12, in patients with high adherence, and in patients receiving weight-appropriate ribavirin dosages. The most common side effects are manageable and include fatigue, headache, myalgia, rigors, fever, nausea, insomnia, and depression. Neutropenia associated with interferon and anemia associated with ribavirin are more serious side effects that can cause discontinuation or dose reduction. Clinicians can maximize results and reduce costs with a regimen of peginterferon alfa plus ribavirin by choosing patients carefully, educating patients thoroughly, stopping therapy early in those patients who do not respond by week 12 of therapy, and enhancing adherence by managing side effects with appropriate dose reductions and/or selective use of antidepressants or hematopoietic colony stimulators.
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PMID:Managing hepatitis C. 1508 65


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